Vaccination of patients with cutaneous melanoma with telomerase-specific peptides
Identifieur interne : 002504 ( Main/Exploration ); précédent : 002503; suivant : 002505Vaccination of patients with cutaneous melanoma with telomerase-specific peptides
Auteurs : Robert E. Hunger [Suisse] ; Kristin Kernland Lang [Suisse] ; Carrie J. Markowski [Norvège] ; Sissel Trachsel [Norvège] ; Mona M Ller [Norvège] ; Jon A. Eriksen [Norvège] ; Anne-Marie Rasmussen [Norvège] ; Lasse R. Braathen [Suisse] ; Gustav Gaudernack [Norvège]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2011-11-01.
Descripteurs français
- Wicri :
- topic : Vaccination.
English descriptors
- KwdEn :
Abstract
Abstract: Purpose: A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611–626) and p540 (hTERT: 540–548) using granulocyte–macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma. Experimental design: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated. Results: Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. Conclusion: These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials.
Url:
DOI: 10.1007/s00262-011-1061-z
Affiliations:
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Markowski</name><affiliation wicri:level="3"><country xml:lang="fr">Norvège</country><wicri:regionArea>Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Trachsel, Sissel" sort="Trachsel, Sissel" uniqKey="Trachsel S" first="Sissel" last="Trachsel">Sissel Trachsel</name><affiliation wicri:level="3"><country xml:lang="fr">Norvège</country><wicri:regionArea>Section for Immunotherapy, Department of Immunology, Oslo University Hospital-Radiumhospitalet and University of Oslo, 0310, Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="M Ller, Mona" sort="M Ller, Mona" uniqKey="M Ller M" first="Mona" last="M Ller">Mona M Ller</name><affiliation wicri:level="1"><country xml:lang="fr">Norvège</country><wicri:regionArea>GemVax AS, Porsgrunn</wicri:regionArea><wicri:noRegion>Porsgrunn</wicri:noRegion></affiliation></author><author><name sortKey="Eriksen, Jon A" sort="Eriksen, Jon A" uniqKey="Eriksen J" first="Jon A." last="Eriksen">Jon A. 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Experimental design: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated. Results: Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. Conclusion: These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials.</div></front></TEI><affiliations><list><country><li>Norvège</li><li>Suisse</li></country><region><li>Canton de Berne</li><li>Østlandet</li></region><settlement><li>Berne</li><li>Oslo</li></settlement></list><tree><country name="Suisse"><region name="Canton de Berne"><name sortKey="Hunger, Robert E" sort="Hunger, Robert E" uniqKey="Hunger R" first="Robert E." last="Hunger">Robert E. Hunger</name></region><name sortKey="Braathen, Lasse R" sort="Braathen, Lasse R" uniqKey="Braathen L" first="Lasse R." last="Braathen">Lasse R. Braathen</name><name sortKey="Hunger, Robert E" sort="Hunger, Robert E" uniqKey="Hunger R" first="Robert E." last="Hunger">Robert E. Hunger</name><name sortKey="Kernland Lang, Kristin" sort="Kernland Lang, Kristin" uniqKey="Kernland Lang K" first="Kristin" last="Kernland Lang">Kristin Kernland Lang</name></country><country name="Norvège"><region name="Østlandet"><name sortKey="Markowski, Carrie J" sort="Markowski, Carrie J" uniqKey="Markowski C" first="Carrie J." last="Markowski">Carrie J. Markowski</name></region><name sortKey="Eriksen, Jon A" sort="Eriksen, Jon A" uniqKey="Eriksen J" first="Jon A." last="Eriksen">Jon A. Eriksen</name><name sortKey="Gaudernack, Gustav" sort="Gaudernack, Gustav" uniqKey="Gaudernack G" first="Gustav" last="Gaudernack">Gustav Gaudernack</name><name sortKey="M Ller, Mona" sort="M Ller, Mona" uniqKey="M Ller M" first="Mona" last="M Ller">Mona M Ller</name><name sortKey="Rasmussen, Anne Marie" sort="Rasmussen, Anne Marie" uniqKey="Rasmussen A" first="Anne-Marie" last="Rasmussen">Anne-Marie Rasmussen</name><name sortKey="Trachsel, Sissel" sort="Trachsel, Sissel" uniqKey="Trachsel S" first="Sissel" last="Trachsel">Sissel Trachsel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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