Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients
Identifieur interne : 006817 ( Ncbi/Merge ); précédent : 006816; suivant : 006818Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients
Auteurs : Ryuji Takahashi [Japon] ; Uhi Toh [Japon] ; Nobutaka Iwakuma [Japon] ; Miki Takenaka [Japon] ; Hiroko Otsuka [Japon] ; Mina Furukawa [Japon] ; Teruhiko Fujii [Japon] ; Naoko Seki [Japon] ; Akihiko Kawahara [Japon] ; Masayoshi Kage [Japon] ; Satoko Matsueda [Japon] ; Yoshito Akagi [Japon] ; Akira Yamada [Japon] ; Kyogo Itoh [Japon] ; Tetsuro Sasada [Japon]Source :
- Breast Cancer Research : BCR [ 1465-5411 ] ; 2014.
Abstract
Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.
Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.
No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.
PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.
Url:
DOI: 10.1186/bcr3685
PubMed: 24992895
PubMed Central: 4227005
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<author><name sortKey="Iwakuma, Nobutaka" sort="Iwakuma, Nobutaka" uniqKey="Iwakuma N" first="Nobutaka" last="Iwakuma">Nobutaka Iwakuma</name>
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<author><name sortKey="Furukawa, Mina" sort="Furukawa, Mina" uniqKey="Furukawa M" first="Mina" last="Furukawa">Mina Furukawa</name>
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<author><name sortKey="Fujii, Teruhiko" sort="Fujii, Teruhiko" uniqKey="Fujii T" first="Teruhiko" last="Fujii">Teruhiko Fujii</name>
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<author><name sortKey="Seki, Naoko" sort="Seki, Naoko" uniqKey="Seki N" first="Naoko" last="Seki">Naoko Seki</name>
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<author><name sortKey="Matsueda, Satoko" sort="Matsueda, Satoko" uniqKey="Matsueda S" first="Satoko" last="Matsueda">Satoko Matsueda</name>
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<author><name sortKey="Otsuka, Hiroko" sort="Otsuka, Hiroko" uniqKey="Otsuka H" first="Hiroko" last="Otsuka">Hiroko Otsuka</name>
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<author><name sortKey="Furukawa, Mina" sort="Furukawa, Mina" uniqKey="Furukawa M" first="Mina" last="Furukawa">Mina Furukawa</name>
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<author><name sortKey="Fujii, Teruhiko" sort="Fujii, Teruhiko" uniqKey="Fujii T" first="Teruhiko" last="Fujii">Teruhiko Fujii</name>
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<author><name sortKey="Seki, Naoko" sort="Seki, Naoko" uniqKey="Seki N" first="Naoko" last="Seki">Naoko Seki</name>
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<author><name sortKey="Kawahara, Akihiko" sort="Kawahara, Akihiko" uniqKey="Kawahara A" first="Akihiko" last="Kawahara">Akihiko Kawahara</name>
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<author><name sortKey="Kage, Masayoshi" sort="Kage, Masayoshi" uniqKey="Kage M" first="Masayoshi" last="Kage">Masayoshi Kage</name>
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<country xml:lang="fr">Japon</country>
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<author><name sortKey="Matsueda, Satoko" sort="Matsueda, Satoko" uniqKey="Matsueda S" first="Satoko" last="Matsueda">Satoko Matsueda</name>
<affiliation wicri:level="1"><nlm:aff id="I4">Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011</wicri:regionArea>
<wicri:noRegion>Kurume 830-0011</wicri:noRegion>
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<author><name sortKey="Akagi, Yoshito" sort="Akagi, Yoshito" uniqKey="Akagi Y" first="Yoshito" last="Akagi">Yoshito Akagi</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011</wicri:regionArea>
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<author><name sortKey="Yamada, Akira" sort="Yamada, Akira" uniqKey="Yamada A" first="Akira" last="Yamada">Akira Yamada</name>
<affiliation wicri:level="1"><nlm:aff id="I2">Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011</wicri:regionArea>
<wicri:noRegion>Kurume 830-0011</wicri:noRegion>
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<author><name sortKey="Itoh, Kyogo" sort="Itoh, Kyogo" uniqKey="Itoh K" first="Kyogo" last="Itoh">Kyogo Itoh</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011</wicri:regionArea>
<wicri:noRegion>Kurume 830-0011</wicri:noRegion>
</affiliation>
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<author><name sortKey="Sasada, Tetsuro" sort="Sasada, Tetsuro" uniqKey="Sasada T" first="Tetsuro" last="Sasada">Tetsuro Sasada</name>
<affiliation wicri:level="1"><nlm:aff id="I4">Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
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<series><title level="j">Breast Cancer Research : BCR</title>
<idno type="ISSN">1465-5411</idno>
<idno type="eISSN">1465-542X</idno>
<imprint><date when="2014">2014</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Introduction</title>
<p>Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.</p>
</sec>
<sec><title>Methods</title>
<p>Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.</p>
</sec>
<sec><title>Results</title>
<p>No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.</p>
</sec>
<sec><title>Conclusions</title>
<p>PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.</p>
</sec>
<sec><title>Clinical Trial Registration Number</title>
<p><ext-link ext-link-type="uri" xlink:href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=history&action=list&type=summary&recptno=R000002216&language=E">UMIN000001844</ext-link>
(Registration Date: April 5, 2009)</p>
</sec>
</div>
</front>
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</TEI>
<pmc article-type="research-article" xml:lang="en"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Breast Cancer Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Breast Cancer Res</journal-id>
<journal-title-group><journal-title>Breast Cancer Research : BCR</journal-title>
</journal-title-group>
<issn pub-type="ppub">1465-5411</issn>
<issn pub-type="epub">1465-542X</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24992895</article-id>
<article-id pub-id-type="pmc">4227005</article-id>
<article-id pub-id-type="publisher-id">bcr3685</article-id>
<article-id pub-id-type="doi">10.1186/bcr3685</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Takahashi</surname>
<given-names>Ryuji</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>takahashi_ryuuji@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" corresp="yes" id="A2"><name><surname>Toh</surname>
<given-names>Uhi</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>utoh@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A3"><name><surname>Iwakuma</surname>
<given-names>Nobutaka</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>iwakuma@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A4"><name><surname>Takenaka</surname>
<given-names>Miki</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>takenaka_miki@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A5"><name><surname>Otsuka</surname>
<given-names>Hiroko</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>hirokotuka@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A6"><name><surname>Furukawa</surname>
<given-names>Mina</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>furukawa_mina@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A7"><name><surname>Fujii</surname>
<given-names>Teruhiko</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>tfujii@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A8"><name><surname>Seki</surname>
<given-names>Naoko</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>seki_naoko@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A9"><name><surname>Kawahara</surname>
<given-names>Akihiko</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<email>akihiko4@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A10"><name><surname>Kage</surname>
<given-names>Masayoshi</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<email>masakage@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A11"><name><surname>Matsueda</surname>
<given-names>Satoko</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>pines@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A12"><name><surname>Akagi</surname>
<given-names>Yoshito</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>yoshisg@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A13"><name><surname>Yamada</surname>
<given-names>Akira</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>akiymd@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A14"><name><surname>Itoh</surname>
<given-names>Kyogo</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>kyogo@med.kurume-u.ac.jp</email>
</contrib>
<contrib contrib-type="author" id="A15"><name><surname>Sasada</surname>
<given-names>Tetsuro</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>tsasada@med.kurume-u.ac.jp</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</aff>
<aff id="I2"><label>2</label>
Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</aff>
<aff id="I3"><label>3</label>
Department of Pathology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</aff>
<aff id="I4"><label>4</label>
Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan</aff>
<pub-date pub-type="ppub"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>7</month>
<year>2014</year>
</pub-date>
<volume>16</volume>
<issue>4</issue>
<fpage>R70</fpage>
<lpage>R70</lpage>
<history><date date-type="received"><day>8</day>
<month>10</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>23</day>
<month>6</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014 Takahashi et al.; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>Takahashi et al.; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://breast-cancer-research.com/content/16/4/R70"></self-uri>
<abstract><sec><title>Introduction</title>
<p>Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.</p>
</sec>
<sec><title>Methods</title>
<p>Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.</p>
</sec>
<sec><title>Results</title>
<p>No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.</p>
</sec>
<sec><title>Conclusions</title>
<p>PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.</p>
</sec>
<sec><title>Clinical Trial Registration Number</title>
<p><ext-link ext-link-type="uri" xlink:href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=history&action=list&type=summary&recptno=R000002216&language=E">UMIN000001844</ext-link>
(Registration Date: April 5, 2009)</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Japon</li>
</country>
</list>
<tree><country name="Japon"><noRegion><name sortKey="Takahashi, Ryuji" sort="Takahashi, Ryuji" uniqKey="Takahashi R" first="Ryuji" last="Takahashi">Ryuji Takahashi</name>
</noRegion>
<name sortKey="Akagi, Yoshito" sort="Akagi, Yoshito" uniqKey="Akagi Y" first="Yoshito" last="Akagi">Yoshito Akagi</name>
<name sortKey="Fujii, Teruhiko" sort="Fujii, Teruhiko" uniqKey="Fujii T" first="Teruhiko" last="Fujii">Teruhiko Fujii</name>
<name sortKey="Furukawa, Mina" sort="Furukawa, Mina" uniqKey="Furukawa M" first="Mina" last="Furukawa">Mina Furukawa</name>
<name sortKey="Itoh, Kyogo" sort="Itoh, Kyogo" uniqKey="Itoh K" first="Kyogo" last="Itoh">Kyogo Itoh</name>
<name sortKey="Iwakuma, Nobutaka" sort="Iwakuma, Nobutaka" uniqKey="Iwakuma N" first="Nobutaka" last="Iwakuma">Nobutaka Iwakuma</name>
<name sortKey="Kage, Masayoshi" sort="Kage, Masayoshi" uniqKey="Kage M" first="Masayoshi" last="Kage">Masayoshi Kage</name>
<name sortKey="Kawahara, Akihiko" sort="Kawahara, Akihiko" uniqKey="Kawahara A" first="Akihiko" last="Kawahara">Akihiko Kawahara</name>
<name sortKey="Matsueda, Satoko" sort="Matsueda, Satoko" uniqKey="Matsueda S" first="Satoko" last="Matsueda">Satoko Matsueda</name>
<name sortKey="Otsuka, Hiroko" sort="Otsuka, Hiroko" uniqKey="Otsuka H" first="Hiroko" last="Otsuka">Hiroko Otsuka</name>
<name sortKey="Sasada, Tetsuro" sort="Sasada, Tetsuro" uniqKey="Sasada T" first="Tetsuro" last="Sasada">Tetsuro Sasada</name>
<name sortKey="Seki, Naoko" sort="Seki, Naoko" uniqKey="Seki N" first="Naoko" last="Seki">Naoko Seki</name>
<name sortKey="Takenaka, Miki" sort="Takenaka, Miki" uniqKey="Takenaka M" first="Miki" last="Takenaka">Miki Takenaka</name>
<name sortKey="Toh, Uhi" sort="Toh, Uhi" uniqKey="Toh U" first="Uhi" last="Toh">Uhi Toh</name>
<name sortKey="Yamada, Akira" sort="Yamada, Akira" uniqKey="Yamada A" first="Akira" last="Yamada">Akira Yamada</name>
</country>
</tree>
</affiliations>
</record>
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