Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909
Identifieur interne : 002694 ( Main/Exploration ); précédent : 002693; suivant : 002695Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909
Auteurs : Jürgen Kuball [Pays-Bas] ; Karin De Boer [Pays-Bas] ; Eva Wagner [Allemagne] ; Mohammed Wattad [Allemagne] ; Edite Antunes [Allemagne] ; Risini D. Weeratna [Canada] ; Alain P. Vicari [Canada, Suisse] ; Carina Lotz [Pays-Bas] ; Suzanne Van Dorp [Pays-Bas] ; Samantha Hol [Pays-Bas] ; Philip D. Greenberg [États-Unis] ; Wolfgang Heit [Allemagne] ; Heather L. Davis [Canada] ; Matthias Theobald [Allemagne]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2011-02-01.
Descripteurs français
- Wicri :
- topic : Vaccination.
English descriptors
Abstract
Abstract: T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8+ T cells was observed. An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration.
Url:
DOI: 10.1007/s00262-010-0929-7
Affiliations:
- Allemagne, Canada, Pays-Bas, Suisse, États-Unis
- Rhénanie-Palatinat, Utrecht (province)
- Mayence, Utrecht
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Weeratna</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pfizer Vaccine Research, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Vicari, Alain P" sort="Vicari, Alain P" uniqKey="Vicari A" first="Alain P." last="Vicari">Alain P. Vicari</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pfizer Vaccine Research, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>Merck Serono S.A., Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Lotz, Carina" sort="Lotz, Carina" uniqKey="Lotz C" first="Carina" last="Lotz">Carina Lotz</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Hematology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Van Dorp, Suzanne" sort="Van Dorp, Suzanne" uniqKey="Van Dorp S" first="Suzanne" last="Van Dorp">Suzanne Van Dorp</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Hematology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Hol, Samantha" sort="Hol, Samantha" uniqKey="Hol S" first="Samantha" last="Hol">Samantha Hol</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Hematology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, University Medical Center Utrecht, Huispostnr.: KC02.085.2, Lundlaan 6, 3584 EA, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Greenberg, Philip D" sort="Greenberg, Philip D" uniqKey="Greenberg P" first="Philip D." last="Greenberg">Philip D. Greenberg</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Program in Immunology, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA</wicri:regionArea><wicri:noRegion>WA</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology, University of Washington School of Medicine, 98195, Seattle, WA</wicri:regionArea><wicri:noRegion>WA</wicri:noRegion></affiliation></author><author><name sortKey="Heit, Wolfgang" sort="Heit, Wolfgang" uniqKey="Heit W" first="Wolfgang" last="Heit">Wolfgang Heit</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Hematology, Kliniken Essen Süd, Essen</wicri:regionArea><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Davis, Heather L" sort="Davis, Heather L" uniqKey="Davis H" first="Heather L." last="Davis">Heather L. Davis</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Pfizer Vaccine Research, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Theobald, Matthias" sort="Theobald, Matthias" uniqKey="Theobald M" first="Matthias" last="Theobald">Matthias Theobald</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Hematology, Johannes Gutenberg-University, Mainz</wicri:regionArea><placeName><region type="land" nuts="2">Rhénanie-Palatinat</region><settlement type="city">Mayence</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Cancer Immunology, Immunotherapy</title><title level="j" type="abbrev">Cancer Immunol Immunother</title><idno type="ISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2011-02-01">2011-02-01</date><biblScope unit="volume">60</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="161">161</biblScope><biblScope unit="page" to="171">171</biblScope></imprint><idno type="ISSN">0340-7004</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-7004</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AML</term><term>CpG</term><term>MM</term><term>T cell</term><term>Vaccination</term><term>WT1</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccination</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8+ T cells was observed. An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Pays-Bas</li><li>Suisse</li><li>États-Unis</li></country><region><li>Rhénanie-Palatinat</li><li>Utrecht (province)</li></region><settlement><li>Mayence</li><li>Utrecht</li></settlement></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Kuball, Jurgen" sort="Kuball, Jurgen" uniqKey="Kuball J" first="Jürgen" last="Kuball">Jürgen Kuball</name></region><name sortKey="De Boer, Karin" sort="De Boer, Karin" uniqKey="De Boer K" first="Karin" last="De Boer">Karin De Boer</name><name sortKey="De Boer, Karin" sort="De Boer, Karin" uniqKey="De Boer K" first="Karin" last="De Boer">Karin De Boer</name><name sortKey="Hol, Samantha" sort="Hol, Samantha" uniqKey="Hol S" first="Samantha" last="Hol">Samantha Hol</name><name sortKey="Hol, Samantha" sort="Hol, Samantha" uniqKey="Hol S" first="Samantha" last="Hol">Samantha Hol</name><name sortKey="Kuball, Jurgen" sort="Kuball, Jurgen" uniqKey="Kuball J" first="Jürgen" last="Kuball">Jürgen Kuball</name><name sortKey="Kuball, Jurgen" sort="Kuball, Jurgen" uniqKey="Kuball J" first="Jürgen" last="Kuball">Jürgen Kuball</name><name sortKey="Lotz, Carina" sort="Lotz, Carina" uniqKey="Lotz C" first="Carina" last="Lotz">Carina Lotz</name><name sortKey="Lotz, Carina" sort="Lotz, Carina" uniqKey="Lotz C" first="Carina" last="Lotz">Carina Lotz</name><name sortKey="Van Dorp, Suzanne" sort="Van Dorp, Suzanne" uniqKey="Van Dorp S" first="Suzanne" last="Van Dorp">Suzanne Van Dorp</name><name sortKey="Van Dorp, Suzanne" sort="Van Dorp, Suzanne" uniqKey="Van Dorp S" first="Suzanne" last="Van Dorp">Suzanne Van Dorp</name></country><country name="Allemagne"><region name="Rhénanie-Palatinat"><name sortKey="Wagner, Eva" sort="Wagner, Eva" uniqKey="Wagner E" first="Eva" last="Wagner">Eva Wagner</name></region><name sortKey="Antunes, Edite" sort="Antunes, Edite" uniqKey="Antunes E" first="Edite" last="Antunes">Edite Antunes</name><name sortKey="Heit, Wolfgang" sort="Heit, Wolfgang" uniqKey="Heit W" first="Wolfgang" last="Heit">Wolfgang Heit</name><name sortKey="Theobald, Matthias" sort="Theobald, Matthias" uniqKey="Theobald M" first="Matthias" last="Theobald">Matthias Theobald</name><name sortKey="Wattad, Mohammed" sort="Wattad, Mohammed" uniqKey="Wattad M" first="Mohammed" last="Wattad">Mohammed Wattad</name></country><country name="Canada"><noRegion><name sortKey="Weeratna, Risini D" sort="Weeratna, Risini D" uniqKey="Weeratna R" first="Risini D." last="Weeratna">Risini D. Weeratna</name></noRegion><name sortKey="Davis, Heather L" sort="Davis, Heather L" uniqKey="Davis H" first="Heather L." last="Davis">Heather L. Davis</name><name sortKey="Vicari, Alain P" sort="Vicari, Alain P" uniqKey="Vicari A" first="Alain P." last="Vicari">Alain P. Vicari</name></country><country name="Suisse"><noRegion><name sortKey="Vicari, Alain P" sort="Vicari, Alain P" uniqKey="Vicari A" first="Alain P." last="Vicari">Alain P. Vicari</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Greenberg, Philip D" sort="Greenberg, Philip D" uniqKey="Greenberg P" first="Philip D." last="Greenberg">Philip D. Greenberg</name></noRegion><name sortKey="Greenberg, Philip D" sort="Greenberg, Philip D" uniqKey="Greenberg P" first="Philip D." last="Greenberg">Philip D. Greenberg</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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