Title |
Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine
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Published in |
Cancer Immunology, Immunotherapy, April 2014
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DOI | 10.1007/s00262-014-1551-x |
Pubmed ID | |
Authors |
Yinin Hu, Gina R. Petroni, Walter C. Olson, Andrea Czarkowski, Mark E. Smolkin, William W. Grosh, Kimberly A. Chianese-Bullock, Craig L. Slingluff |
Abstract |
Immunization with a combination melanoma helper peptide (6MHP) vaccine has been shown to induce CD4(+) T cell responses, which are associated with patient survival. In the present study, we define the relative immunogenicity and HLA allele promiscuity of individual helper peptides and identify helper peptide-mediated augmentation of specific CD8(+) T cell responses. Thirty-seven participants with stage IIIB-IV melanoma were vaccinated with 6MHP in incomplete Freund's adjuvant. The 6MHP vaccine is comprised of 6 peptides representing melanocytic differentiation proteins gp100, tyrosinase, Melan-A/MART-1, and cancer testis antigens from the MAGE family. CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by thymidine uptake after exposure to helper peptides and by direct interferon-γ ELIspot assay against 14 MHC class I-restricted peptides. Vaccine-induced CD4(+) T cell responses to individual epitopes were detected in the SIN of 63 % (22/35) and in the peripheral blood of 38 % (14/37) of participants for an overall response rate of 65 % (24/37). The most frequently immunogenic peptides were MAGE-A3281-295 (49 %) and tyrosinase386-406 (32 %). Responses were not limited to HLA restrictions originally described. Vaccine-associated CD8(+) T cell responses against class I-restricted peptides were observed in 45 % (5/11) of evaluable participants. The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens. CD4(+) T cell responses were detected beyond reported HLA-DR restrictions. Induction of CD8(+) T cell responses suggests epitope spreading and systemic activity mediated at the tumor site. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 37 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 9 | 24% |
Student > Ph. D. Student | 8 | 22% |
Student > Master | 5 | 14% |
Student > Bachelor | 3 | 8% |
Other | 3 | 8% |
Other | 4 | 11% |
Unknown | 5 | 14% |
Readers by discipline | Count | As % |
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Immunology and Microbiology | 11 | 30% |
Agricultural and Biological Sciences | 8 | 22% |
Medicine and Dentistry | 5 | 14% |
Biochemistry, Genetics and Molecular Biology | 3 | 8% |
Engineering | 2 | 5% |
Other | 1 | 3% |
Unknown | 7 | 19% |