A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2+ Metastatic Breast Cancer
Identifieur interne : 002E99 ( Ncbi/Merge ); précédent : 002E98; suivant : 002F00A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2+ Metastatic Breast Cancer
Auteurs : G. Chen ; R. Gupta ; S. Petrik ; M. Laiko ; Jm Leatherman ; Jm Asquith ; Mm Daphtary ; E. Garrett-Mayer ; Ne Davidson ; K. Hirt ; M. Berg ; Jn Uram ; T. Dauses ; J. Fetting ; Em Duus ; S. Atay-Rosenthal ; X. Ye ; Ac Wolff ; V. Stearns ; Em Jaffee ; La EmensSource :
- Cancer immunology research [ 2326-6066 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse de survie, Animaux, Anticorps monoclonaux humanisés (administration et posologie), Anticorps monoclonaux humanisés (effets indésirables), Antinéoplasiques (effets indésirables), Antinéoplasiques (usage thérapeutique), Association thérapeutique, Cyclophosphamide (administration et posologie), Cyclophosphamide (effets indésirables), Facteur de stimulation des colonies de granulocytes et de macrophages (métabolisme), Femelle, Humains, Hypersensibilité retardée (immunologie), Lignée cellulaire tumorale, Lymphocytes T CD8+ (immunologie), Métastase tumorale, Récepteur ErbB-2 (immunologie), Récepteur ErbB-2 (métabolisme), Souris transgéniques, Sujet âgé, Trastuzumab, Tumeurs du sein (), Tumeurs du sein (immunologie), Tumeurs du sein (métabolisme), Vaccins anticancéreux (effets indésirables), Vaccins anticancéreux (immunologie), Vaccins anticancéreux (usage thérapeutique), Études de faisabilité.
- MESH :
- administration et posologie : Anticorps monoclonaux humanisés, Cyclophosphamide.
- effets indésirables : Anticorps monoclonaux humanisés, Antinéoplasiques, Cyclophosphamide, Vaccins anticancéreux.
- immunologie : Hypersensibilité retardée, Lymphocytes T CD8+, Récepteur ErbB-2, Tumeurs du sein, Vaccins anticancéreux.
- métabolisme : Facteur de stimulation des colonies de granulocytes et de macrophages, Récepteur ErbB-2, Tumeurs du sein.
- usage thérapeutique : Antinéoplasiques, Vaccins anticancéreux.
- Adulte, Adulte d'âge moyen, Analyse de survie, Animaux, Association thérapeutique, Femelle, Humains, Lignée cellulaire tumorale, Métastase tumorale, Souris transgéniques, Sujet âgé, Trastuzumab, Tumeurs du sein, Études de faisabilité.
English descriptors
- KwdEn :
- Adult, Aged, Animals, Antibodies, Monoclonal, Humanized (administration & dosage), Antibodies, Monoclonal, Humanized (adverse effects), Antineoplastic Agents (adverse effects), Antineoplastic Agents (therapeutic use), Breast Neoplasms (immunology), Breast Neoplasms (metabolism), Breast Neoplasms (therapy), CD8-Positive T-Lymphocytes (immunology), Cancer Vaccines (adverse effects), Cancer Vaccines (immunology), Cancer Vaccines (therapeutic use), Cell Line, Tumor, Combined Modality Therapy, Cyclophosphamide (administration & dosage), Cyclophosphamide (adverse effects), Feasibility Studies, Female, Granulocyte-Macrophage Colony-Stimulating Factor (metabolism), Humans, Hypersensitivity, Delayed (immunology), Mice, Transgenic, Middle Aged, Neoplasm Metastasis, Receptor, ErbB-2 (immunology), Receptor, ErbB-2 (metabolism), Survival Analysis, Trastuzumab.
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Humanized, Cyclophosphamide.
- chemical , adverse effects : Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Cancer Vaccines, Cyclophosphamide.
- chemical , immunology : Cancer Vaccines, Receptor, ErbB-2.
- chemical , metabolism : Granulocyte-Macrophage Colony-Stimulating Factor, Receptor, ErbB-2.
- chemical , therapeutic use : Antineoplastic Agents, Cancer Vaccines.
- immunology : Breast Neoplasms, CD8-Positive T-Lymphocytes, Hypersensitivity, Delayed.
- metabolism : Breast Neoplasms.
- therapy : Breast Neoplasms.
- Adult, Aged, Animals, Cell Line, Tumor, Combined Modality Therapy, Feasibility Studies, Female, Humans, Mice, Transgenic, Middle Aged, Neoplasm Metastasis, Survival Analysis, Trastuzumab.
Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide (CY) augments vaccine activity in tolerant
Url:
DOI: 10.1158/2326-6066.CIR-14-0058
PubMed: 25116755
PubMed Central: 4211036
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PMC:4211036Le document en format XML
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Chen</name></author><author><name sortKey="Gupta, R" sort="Gupta, R" uniqKey="Gupta R" first="R" last="Gupta">R. Gupta</name></author><author><name sortKey="Petrik, S" sort="Petrik, S" uniqKey="Petrik S" first="S" last="Petrik">S. Petrik</name></author><author><name sortKey="Laiko, M" sort="Laiko, M" uniqKey="Laiko M" first="M" last="Laiko">M. Laiko</name></author><author><name sortKey="Leatherman, Jm" sort="Leatherman, Jm" uniqKey="Leatherman J" first="Jm" last="Leatherman">Jm Leatherman</name></author><author><name sortKey="Asquith, Jm" sort="Asquith, Jm" uniqKey="Asquith J" first="Jm" last="Asquith">Jm Asquith</name></author><author><name sortKey="Daphtary, Mm" sort="Daphtary, Mm" uniqKey="Daphtary M" first="Mm" last="Daphtary">Mm Daphtary</name></author><author><name sortKey="Garrett Mayer, E" sort="Garrett Mayer, E" uniqKey="Garrett Mayer E" first="E" last="Garrett-Mayer">E. Garrett-Mayer</name></author><author><name sortKey="Davidson, Ne" sort="Davidson, Ne" uniqKey="Davidson N" first="Ne" last="Davidson">Ne Davidson</name></author><author><name sortKey="Hirt, K" sort="Hirt, K" uniqKey="Hirt K" first="K" last="Hirt">K. Hirt</name></author><author><name sortKey="Berg, M" sort="Berg, M" uniqKey="Berg M" first="M" last="Berg">M. Berg</name></author><author><name sortKey="Uram, Jn" sort="Uram, Jn" uniqKey="Uram J" first="Jn" last="Uram">Jn Uram</name></author><author><name sortKey="Dauses, T" sort="Dauses, T" uniqKey="Dauses T" first="T" last="Dauses">T. Dauses</name></author><author><name sortKey="Fetting, J" sort="Fetting, J" uniqKey="Fetting J" first="J" last="Fetting">J. Fetting</name></author><author><name sortKey="Duus, Em" sort="Duus, Em" uniqKey="Duus E" first="Em" last="Duus">Em Duus</name></author><author><name sortKey="Atay Rosenthal, S" sort="Atay Rosenthal, S" uniqKey="Atay Rosenthal S" first="S" last="Atay-Rosenthal">S. Atay-Rosenthal</name></author><author><name sortKey="Ye, X" sort="Ye, X" uniqKey="Ye X" first="X" last="Ye">X. Ye</name></author><author><name sortKey="Wolff, Ac" sort="Wolff, Ac" uniqKey="Wolff A" first="Ac" last="Wolff">Ac Wolff</name></author><author><name sortKey="Stearns, V" sort="Stearns, V" uniqKey="Stearns V" first="V" last="Stearns">V. Stearns</name></author><author><name sortKey="Jaffee, Em" sort="Jaffee, Em" uniqKey="Jaffee E" first="Em" last="Jaffee">Em Jaffee</name></author><author><name sortKey="Emens, La" sort="Emens, La" uniqKey="Emens L" first="La" last="Emens">La Emens</name></author></analytic><series><title level="j">Cancer immunology research</title><idno type="ISSN">2326-6066</idno><idno type="eISSN">2326-6074</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Antibodies, Monoclonal, Humanized (administration & dosage)</term><term>Antibodies, Monoclonal, Humanized (adverse effects)</term><term>Antineoplastic Agents (adverse effects)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Breast Neoplasms (immunology)</term><term>Breast Neoplasms (metabolism)</term><term>Breast Neoplasms (therapy)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cancer Vaccines (adverse effects)</term><term>Cancer Vaccines (immunology)</term><term>Cancer Vaccines (therapeutic use)</term><term>Cell Line, Tumor</term><term>Combined Modality Therapy</term><term>Cyclophosphamide (administration & dosage)</term><term>Cyclophosphamide (adverse effects)</term><term>Feasibility Studies</term><term>Female</term><term>Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)</term><term>Humans</term><term>Hypersensitivity, Delayed (immunology)</term><term>Mice, Transgenic</term><term>Middle Aged</term><term>Neoplasm Metastasis</term><term>Receptor, ErbB-2 (immunology)</term><term>Receptor, ErbB-2 (metabolism)</term><term>Survival Analysis</term><term>Trastuzumab</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de survie</term><term>Animaux</term><term>Anticorps monoclonaux humanisés (administration et posologie)</term><term>Anticorps monoclonaux humanisés (effets indésirables)</term><term>Antinéoplasiques (effets indésirables)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Association thérapeutique</term><term>Cyclophosphamide (administration et posologie)</term><term>Cyclophosphamide (effets indésirables)</term><term>Facteur de stimulation des colonies de granulocytes et de macrophages (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Hypersensibilité retardée (immunologie)</term><term>Lignée cellulaire tumorale</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Métastase tumorale</term><term>Récepteur ErbB-2 (immunologie)</term><term>Récepteur ErbB-2 (métabolisme)</term><term>Souris transgéniques</term><term>Sujet âgé</term><term>Trastuzumab</term><term>Tumeurs du sein ()</term><term>Tumeurs du sein (immunologie)</term><term>Tumeurs du sein (métabolisme)</term><term>Vaccins anticancéreux (effets indésirables)</term><term>Vaccins anticancéreux (immunologie)</term><term>Vaccins anticancéreux (usage thérapeutique)</term><term>Études de faisabilité</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents</term><term>Cancer Vaccines</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Cancer Vaccines</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Granulocyte-Macrophage Colony-Stimulating Factor</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Cancer Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antinéoplasiques</term><term>Cyclophosphamide</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Hypersensibilité retardée</term><term>Lymphocytes T CD8+</term><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Breast Neoplasms</term><term>CD8-Positive T-Lymphocytes</term><term>Hypersensitivity, Delayed</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de stimulation des colonies de granulocytes et de macrophages</term><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Cell Line, Tumor</term><term>Combined Modality Therapy</term><term>Feasibility Studies</term><term>Female</term><term>Humans</term><term>Mice, Transgenic</term><term>Middle Aged</term><term>Neoplasm Metastasis</term><term>Survival Analysis</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de survie</term><term>Animaux</term><term>Association thérapeutique</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Métastase tumorale</term><term>Souris transgéniques</term><term>Sujet âgé</term><term>Trastuzumab</term><term>Tumeurs du sein</term><term>Études de faisabilité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide (CY) augments vaccine activity in tolerant <italic>neu</italic> mice and metastatic breast cancer (MBC) patients. HER-2-specific monoclonal antibodies (MAb) enhance vaccine activity in <italic>neu</italic> mice. We hypothesized that CY-modulated vaccination with HER-2-specific MAb safely induces relevant HER-2-specific immunity in <italic>neu</italic> mice and HER-2<sup>+</sup> MBC patients. Adding both CY and the HER-2-specific MAb 7.16.4 to vaccination maximized HER-2-specific CD8<sup>+</sup> T-cell immunity and tumor-free survival in <italic>neu</italic> transgenic mice. We therefore conducted a single arm feasibility study of CY, an allogeneic HER-2<sup>+</sup> GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 HER-2<sup>+</sup> MBC patients. Primary clinical trial objectives were safety and clinical benefit (CB), in which CB represents complete response+partial response+stable disease. Secondary study objectives were to assess HER-2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Subjects received three monthly vaccinations, with a boost 6-8 months from trial entry. This combination immunotherapy was safe, with CB rates at 6 months and 1 year of 55% (95% CI:32-77%, p=0.013) and 40% (95% CI:19-64%) respectively. Median progression-free survival (PFS) and overall survival (OS) were 7 (95% CI:4-16) and 42 months (95% CI:22-70) respectively. Increased HER-2-specific DTH developed in 7/20 subjects (of whom 4 had CB (95% CI:18-90)), with a trend toward longer PFS and OS in DTH responders. Polyfunctional HER-2-specific CD8<sup>+</sup> T cells progressively expanded across vaccination cycles. Further investigation of CY-modulated vaccination with trastuzumab is warranted. (<ext-link ext-link-type="uri" xlink:href="http://Clinicaltrials.gov">Clinicaltrials.gov</ext-link> identifier: NCT00399529)</p></div></front></TEI><double pmid="25116755"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2<sup>+</sup> Metastatic Breast Cancer</title><author><name sortKey="Chen, G" sort="Chen, G" uniqKey="Chen G" first="G" last="Chen">G. Chen</name></author><author><name sortKey="Gupta, R" sort="Gupta, R" uniqKey="Gupta R" first="R" last="Gupta">R. Gupta</name></author><author><name sortKey="Petrik, S" sort="Petrik, S" uniqKey="Petrik S" first="S" last="Petrik">S. Petrik</name></author><author><name sortKey="Laiko, M" sort="Laiko, M" uniqKey="Laiko M" first="M" last="Laiko">M. Laiko</name></author><author><name sortKey="Leatherman, Jm" sort="Leatherman, Jm" uniqKey="Leatherman J" first="Jm" last="Leatherman">Jm Leatherman</name></author><author><name sortKey="Asquith, Jm" sort="Asquith, Jm" uniqKey="Asquith J" first="Jm" last="Asquith">Jm Asquith</name></author><author><name sortKey="Daphtary, Mm" sort="Daphtary, Mm" uniqKey="Daphtary M" first="Mm" last="Daphtary">Mm Daphtary</name></author><author><name sortKey="Garrett Mayer, E" sort="Garrett Mayer, E" uniqKey="Garrett Mayer E" first="E" last="Garrett-Mayer">E. Garrett-Mayer</name></author><author><name sortKey="Davidson, Ne" sort="Davidson, Ne" uniqKey="Davidson N" first="Ne" last="Davidson">Ne Davidson</name></author><author><name sortKey="Hirt, K" sort="Hirt, K" uniqKey="Hirt K" first="K" last="Hirt">K. Hirt</name></author><author><name sortKey="Berg, M" sort="Berg, M" uniqKey="Berg M" first="M" last="Berg">M. Berg</name></author><author><name sortKey="Uram, Jn" sort="Uram, Jn" uniqKey="Uram J" first="Jn" last="Uram">Jn Uram</name></author><author><name sortKey="Dauses, T" sort="Dauses, T" uniqKey="Dauses T" first="T" last="Dauses">T. Dauses</name></author><author><name sortKey="Fetting, J" sort="Fetting, J" uniqKey="Fetting J" first="J" last="Fetting">J. Fetting</name></author><author><name sortKey="Duus, Em" sort="Duus, Em" uniqKey="Duus E" first="Em" last="Duus">Em Duus</name></author><author><name sortKey="Atay Rosenthal, S" sort="Atay Rosenthal, S" uniqKey="Atay Rosenthal S" first="S" last="Atay-Rosenthal">S. Atay-Rosenthal</name></author><author><name sortKey="Ye, X" sort="Ye, X" uniqKey="Ye X" first="X" last="Ye">X. Ye</name></author><author><name sortKey="Wolff, Ac" sort="Wolff, Ac" uniqKey="Wolff A" first="Ac" last="Wolff">Ac Wolff</name></author><author><name sortKey="Stearns, V" sort="Stearns, V" uniqKey="Stearns V" first="V" last="Stearns">V. Stearns</name></author><author><name sortKey="Jaffee, Em" sort="Jaffee, Em" uniqKey="Jaffee E" first="Em" last="Jaffee">Em Jaffee</name></author><author><name sortKey="Emens, La" sort="Emens, La" uniqKey="Emens L" first="La" last="Emens">La Emens</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25116755</idno><idno type="pmc">4211036</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211036</idno><idno type="RBID">PMC:4211036</idno><idno type="doi">10.1158/2326-6066.CIR-14-0058</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001215</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001215</idno><idno type="wicri:Area/Pmc/Curation">001190</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001190</idno><idno type="wicri:Area/Pmc/Checkpoint">001E69</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001E69</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2<sup>+</sup> Metastatic Breast Cancer</title><author><name sortKey="Chen, G" sort="Chen, G" uniqKey="Chen G" first="G" last="Chen">G. Chen</name></author><author><name sortKey="Gupta, R" sort="Gupta, R" uniqKey="Gupta R" first="R" last="Gupta">R. Gupta</name></author><author><name sortKey="Petrik, S" sort="Petrik, S" uniqKey="Petrik S" first="S" last="Petrik">S. Petrik</name></author><author><name sortKey="Laiko, M" sort="Laiko, M" uniqKey="Laiko M" first="M" last="Laiko">M. Laiko</name></author><author><name sortKey="Leatherman, Jm" sort="Leatherman, Jm" uniqKey="Leatherman J" first="Jm" last="Leatherman">Jm Leatherman</name></author><author><name sortKey="Asquith, Jm" sort="Asquith, Jm" uniqKey="Asquith J" first="Jm" last="Asquith">Jm Asquith</name></author><author><name sortKey="Daphtary, Mm" sort="Daphtary, Mm" uniqKey="Daphtary M" first="Mm" last="Daphtary">Mm Daphtary</name></author><author><name sortKey="Garrett Mayer, E" sort="Garrett Mayer, E" uniqKey="Garrett Mayer E" first="E" last="Garrett-Mayer">E. Garrett-Mayer</name></author><author><name sortKey="Davidson, Ne" sort="Davidson, Ne" uniqKey="Davidson N" first="Ne" last="Davidson">Ne Davidson</name></author><author><name sortKey="Hirt, K" sort="Hirt, K" uniqKey="Hirt K" first="K" last="Hirt">K. Hirt</name></author><author><name sortKey="Berg, M" sort="Berg, M" uniqKey="Berg M" first="M" last="Berg">M. Berg</name></author><author><name sortKey="Uram, Jn" sort="Uram, Jn" uniqKey="Uram J" first="Jn" last="Uram">Jn Uram</name></author><author><name sortKey="Dauses, T" sort="Dauses, T" uniqKey="Dauses T" first="T" last="Dauses">T. Dauses</name></author><author><name sortKey="Fetting, J" sort="Fetting, J" uniqKey="Fetting J" first="J" last="Fetting">J. Fetting</name></author><author><name sortKey="Duus, Em" sort="Duus, Em" uniqKey="Duus E" first="Em" last="Duus">Em Duus</name></author><author><name sortKey="Atay Rosenthal, S" sort="Atay Rosenthal, S" uniqKey="Atay Rosenthal S" first="S" last="Atay-Rosenthal">S. Atay-Rosenthal</name></author><author><name sortKey="Ye, X" sort="Ye, X" uniqKey="Ye X" first="X" last="Ye">X. Ye</name></author><author><name sortKey="Wolff, Ac" sort="Wolff, Ac" uniqKey="Wolff A" first="Ac" last="Wolff">Ac Wolff</name></author><author><name sortKey="Stearns, V" sort="Stearns, V" uniqKey="Stearns V" first="V" last="Stearns">V. Stearns</name></author><author><name sortKey="Jaffee, Em" sort="Jaffee, Em" uniqKey="Jaffee E" first="Em" last="Jaffee">Em Jaffee</name></author><author><name sortKey="Emens, La" sort="Emens, La" uniqKey="Emens L" first="La" last="Emens">La Emens</name></author></analytic><series><title level="j">Cancer immunology research</title><idno type="ISSN">2326-6066</idno><idno type="eISSN">2326-6074</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide (CY) augments vaccine activity in tolerant <italic>neu</italic> mice and metastatic breast cancer (MBC) patients. HER-2-specific monoclonal antibodies (MAb) enhance vaccine activity in <italic>neu</italic> mice. We hypothesized that CY-modulated vaccination with HER-2-specific MAb safely induces relevant HER-2-specific immunity in <italic>neu</italic> mice and HER-2<sup>+</sup> MBC patients. Adding both CY and the HER-2-specific MAb 7.16.4 to vaccination maximized HER-2-specific CD8<sup>+</sup> T-cell immunity and tumor-free survival in <italic>neu</italic> transgenic mice. We therefore conducted a single arm feasibility study of CY, an allogeneic HER-2<sup>+</sup> GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 HER-2<sup>+</sup> MBC patients. Primary clinical trial objectives were safety and clinical benefit (CB), in which CB represents complete response+partial response+stable disease. Secondary study objectives were to assess HER-2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Subjects received three monthly vaccinations, with a boost 6-8 months from trial entry. This combination immunotherapy was safe, with CB rates at 6 months and 1 year of 55% (95% CI:32-77%, p=0.013) and 40% (95% CI:19-64%) respectively. Median progression-free survival (PFS) and overall survival (OS) were 7 (95% CI:4-16) and 42 months (95% CI:22-70) respectively. Increased HER-2-specific DTH developed in 7/20 subjects (of whom 4 had CB (95% CI:18-90)), with a trend toward longer PFS and OS in DTH responders. Polyfunctional HER-2-specific CD8<sup>+</sup> T cells progressively expanded across vaccination cycles. Further investigation of CY-modulated vaccination with trastuzumab is warranted. (<ext-link ext-link-type="uri" xlink:href="http://Clinicaltrials.gov">Clinicaltrials.gov</ext-link> identifier: NCT00399529)</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.</title><author><name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Gupta, Richa" sort="Gupta, Richa" uniqKey="Gupta R" first="Richa" last="Gupta">Richa Gupta</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Petrik, Silvia" sort="Petrik, Silvia" uniqKey="Petrik S" first="Silvia" last="Petrik">Silvia Petrik</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Laiko, Marina" sort="Laiko, Marina" uniqKey="Laiko M" first="Marina" last="Laiko">Marina Laiko</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Leatherman, James M" sort="Leatherman, James M" uniqKey="Leatherman J" first="James M" last="Leatherman">James M. Leatherman</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Asquith, Justin M" sort="Asquith, Justin M" uniqKey="Asquith J" first="Justin M" last="Asquith">Justin M. Asquith</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Daphtary, Maithili M" sort="Daphtary, Maithili M" uniqKey="Daphtary M" first="Maithili M" last="Daphtary">Maithili M. Daphtary</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Garrett Mayer, Elizabeth" sort="Garrett Mayer, Elizabeth" uniqKey="Garrett Mayer E" first="Elizabeth" last="Garrett-Mayer">Elizabeth Garrett-Mayer</name><affiliation wicri:level="2"><nlm:affiliation>Medical University of South Carolina, Charleston, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>Medical University of South Carolina, Charleston</wicri:cityArea></affiliation></author><author><name sortKey="Davidson, Nancy E" sort="Davidson, Nancy E" uniqKey="Davidson N" first="Nancy E" last="Davidson">Nancy E. Davidson</name><affiliation wicri:level="2"><nlm:affiliation>University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, Pennsylvania.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Hirt, Kellie" sort="Hirt, Kellie" uniqKey="Hirt K" first="Kellie" last="Hirt">Kellie Hirt</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Berg, Maureen" sort="Berg, Maureen" uniqKey="Berg M" first="Maureen" last="Berg">Maureen Berg</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Uram, Jennifer N" sort="Uram, Jennifer N" uniqKey="Uram J" first="Jennifer N" last="Uram">Jennifer N. Uram</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Dauses, Tianna" sort="Dauses, Tianna" uniqKey="Dauses T" first="Tianna" last="Dauses">Tianna Dauses</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Fetting, John" sort="Fetting, John" uniqKey="Fetting J" first="John" last="Fetting">John Fetting</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Duus, Elizabeth M" sort="Duus, Elizabeth M" uniqKey="Duus E" first="Elizabeth M" last="Duus">Elizabeth M. Duus</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Atay Rosenthal, Saadet" sort="Atay Rosenthal, Saadet" uniqKey="Atay Rosenthal S" first="Saadet" last="Atay-Rosenthal">Saadet Atay-Rosenthal</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Ye, Xiaobu" sort="Ye, Xiaobu" uniqKey="Ye X" first="Xiaobu" last="Ye">Xiaobu Ye</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C" last="Wolff">Antonio C. Wolff</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Jaffee, Elizabeth M" sort="Jaffee, Elizabeth M" uniqKey="Jaffee E" first="Elizabeth M" last="Jaffee">Elizabeth M. Jaffee</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Emens, Leisha A" sort="Emens, Leisha A" uniqKey="Emens L" first="Leisha A" last="Emens">Leisha A. Emens</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. emensle@jhmi.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25116755</idno><idno type="pmid">25116755</idno><idno type="doi">10.1158/2326-6066.CIR-14-0058</idno><idno type="wicri:Area/PubMed/Corpus">001673</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001673</idno><idno type="wicri:Area/PubMed/Curation">001666</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001666</idno><idno type="wicri:Area/PubMed/Checkpoint">001666</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001666</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.</title><author><name sortKey="Chen, Gang" sort="Chen, Gang" uniqKey="Chen G" first="Gang" last="Chen">Gang Chen</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Gupta, Richa" sort="Gupta, Richa" uniqKey="Gupta R" first="Richa" last="Gupta">Richa Gupta</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Petrik, Silvia" sort="Petrik, Silvia" uniqKey="Petrik S" first="Silvia" last="Petrik">Silvia Petrik</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Laiko, Marina" sort="Laiko, Marina" uniqKey="Laiko M" first="Marina" last="Laiko">Marina Laiko</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Leatherman, James M" sort="Leatherman, James M" uniqKey="Leatherman J" first="James M" last="Leatherman">James M. Leatherman</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Asquith, Justin M" sort="Asquith, Justin M" uniqKey="Asquith J" first="Justin M" last="Asquith">Justin M. Asquith</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Daphtary, Maithili M" sort="Daphtary, Maithili M" uniqKey="Daphtary M" first="Maithili M" last="Daphtary">Maithili M. Daphtary</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Garrett Mayer, Elizabeth" sort="Garrett Mayer, Elizabeth" uniqKey="Garrett Mayer E" first="Elizabeth" last="Garrett-Mayer">Elizabeth Garrett-Mayer</name><affiliation wicri:level="2"><nlm:affiliation>Medical University of South Carolina, Charleston, South Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Sud</region></placeName><wicri:cityArea>Medical University of South Carolina, Charleston</wicri:cityArea></affiliation></author><author><name sortKey="Davidson, Nancy E" sort="Davidson, Nancy E" uniqKey="Davidson N" first="Nancy E" last="Davidson">Nancy E. Davidson</name><affiliation wicri:level="2"><nlm:affiliation>University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh, Pennsylvania.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>University of Pittsburgh Cancer Institute and UPMC CancerCenter, Pittsburgh</wicri:cityArea></affiliation></author><author><name sortKey="Hirt, Kellie" sort="Hirt, Kellie" uniqKey="Hirt K" first="Kellie" last="Hirt">Kellie Hirt</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Berg, Maureen" sort="Berg, Maureen" uniqKey="Berg M" first="Maureen" last="Berg">Maureen Berg</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Uram, Jennifer N" sort="Uram, Jennifer N" uniqKey="Uram J" first="Jennifer N" last="Uram">Jennifer N. Uram</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Dauses, Tianna" sort="Dauses, Tianna" uniqKey="Dauses T" first="Tianna" last="Dauses">Tianna Dauses</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Fetting, John" sort="Fetting, John" uniqKey="Fetting J" first="John" last="Fetting">John Fetting</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Duus, Elizabeth M" sort="Duus, Elizabeth M" uniqKey="Duus E" first="Elizabeth M" last="Duus">Elizabeth M. Duus</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Atay Rosenthal, Saadet" sort="Atay Rosenthal, Saadet" uniqKey="Atay Rosenthal S" first="Saadet" last="Atay-Rosenthal">Saadet Atay-Rosenthal</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Ye, Xiaobu" sort="Ye, Xiaobu" uniqKey="Ye X" first="Xiaobu" last="Ye">Xiaobu Ye</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C" last="Wolff">Antonio C. Wolff</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Jaffee, Elizabeth M" sort="Jaffee, Elizabeth M" uniqKey="Jaffee E" first="Elizabeth M" last="Jaffee">Elizabeth M. Jaffee</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Emens, Leisha A" sort="Emens, Leisha A" uniqKey="Emens L" first="Leisha A" last="Emens">Leisha A. Emens</name><affiliation wicri:level="2"><nlm:affiliation>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. emensle@jhmi.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Program in Pathobiology, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author></analytic><series><title level="j">Cancer immunology research</title><idno type="eISSN">2326-6074</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Antibodies, Monoclonal, Humanized (administration & dosage)</term><term>Antibodies, Monoclonal, Humanized (adverse effects)</term><term>Antineoplastic Agents (adverse effects)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Breast Neoplasms (immunology)</term><term>Breast Neoplasms (metabolism)</term><term>Breast Neoplasms (therapy)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cancer Vaccines (adverse effects)</term><term>Cancer Vaccines (immunology)</term><term>Cancer Vaccines (therapeutic use)</term><term>Cell Line, Tumor</term><term>Combined Modality Therapy</term><term>Cyclophosphamide (administration & dosage)</term><term>Cyclophosphamide (adverse effects)</term><term>Feasibility Studies</term><term>Female</term><term>Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)</term><term>Humans</term><term>Hypersensitivity, Delayed (immunology)</term><term>Mice, Transgenic</term><term>Middle Aged</term><term>Neoplasm Metastasis</term><term>Receptor, ErbB-2 (immunology)</term><term>Receptor, ErbB-2 (metabolism)</term><term>Survival Analysis</term><term>Trastuzumab</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de survie</term><term>Animaux</term><term>Anticorps monoclonaux humanisés (administration et posologie)</term><term>Anticorps monoclonaux humanisés (effets indésirables)</term><term>Antinéoplasiques (effets indésirables)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Association thérapeutique</term><term>Cyclophosphamide (administration et posologie)</term><term>Cyclophosphamide (effets indésirables)</term><term>Facteur de stimulation des colonies de granulocytes et de macrophages (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Hypersensibilité retardée (immunologie)</term><term>Lignée cellulaire tumorale</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Métastase tumorale</term><term>Récepteur ErbB-2 (immunologie)</term><term>Récepteur ErbB-2 (métabolisme)</term><term>Souris transgéniques</term><term>Sujet âgé</term><term>Trastuzumab</term><term>Tumeurs du sein ()</term><term>Tumeurs du sein (immunologie)</term><term>Tumeurs du sein (métabolisme)</term><term>Vaccins anticancéreux (effets indésirables)</term><term>Vaccins anticancéreux (immunologie)</term><term>Vaccins anticancéreux (usage thérapeutique)</term><term>Études de faisabilité</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents</term><term>Cancer Vaccines</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Cancer Vaccines</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Granulocyte-Macrophage Colony-Stimulating Factor</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Cancer Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Cyclophosphamide</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antinéoplasiques</term><term>Cyclophosphamide</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Hypersensibilité retardée</term><term>Lymphocytes T CD8+</term><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Breast Neoplasms</term><term>CD8-Positive T-Lymphocytes</term><term>Hypersensitivity, Delayed</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de stimulation des colonies de granulocytes et de macrophages</term><term>Récepteur ErbB-2</term><term>Tumeurs du sein</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term><term>Vaccins anticancéreux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Cell Line, Tumor</term><term>Combined Modality Therapy</term><term>Feasibility Studies</term><term>Female</term><term>Humans</term><term>Mice, Transgenic</term><term>Middle Aged</term><term>Neoplasm Metastasis</term><term>Survival Analysis</term><term>Trastuzumab</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de survie</term><term>Animaux</term><term>Association thérapeutique</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Métastase tumorale</term><term>Souris transgéniques</term><term>Sujet âgé</term><term>Trastuzumab</term><term>Tumeurs du sein</term><term>Études de faisabilité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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