TY - JOUR
T1 - Identification of HLA-A*03, A*11 and B*07-restricted melanoma-associated peptides that are immunogenic in vivo by vaccine-induced immune response (VIIR) analysis
AU - Reynolds, Sandra R.
AU - Celis, Esteban
AU - Sette, Alessandro
AU - Oratz, Ruth
AU - Shapiro, Richard L.
AU - Johnston, Dean
AU - Fotino, Marilena
AU - Bystryn, Jean Claude
N1 - Funding Information:
This work was supported in part by NIH grants RO1 AM 27663-09, P30CA16087, R21 CA78659 and R21 CA75317 and by grants from the Rose M. Badgeley Trust and the Gaisman Foundation. We thank Dunlu Chen and Michelene Rivas for vaccine preparation, Elise Kelman for performing ELISPOT assays and Arvind K. Menon for HLA typing.
PY - 2000/10/20
Y1 - 2000/10/20
N2 - With the discovery of increasing numbers of tumor antigens, there is a need to rapidly determine whether these antigens and the individual peptides they express are able to stimulate immune responses in vivo and thus, can be used to construct cancer vaccines. In this study we used the method of vaccine-induced immune response (VIIR) analysis to identify multiple immunogenic peptide epitopes derived from several melanoma associated antigens and presented by HLA-A*03, A*11 and B*07. Thirty-one patients with melanoma were immunized to a polyvalent vaccine containing multiple antigens, including MAGE-3, Melan A/MART-1, gp100 and tyrosinase. Their peripheral blood was tested for peptide-specific, vaccine-induced CD8+ T cell responses before and after immunization using an enzyme-linked immune spot (ELISPOT) assay with panels of peptides restricted by these three alleles. The peptides were selected for immunogenic potential based on their strong binding affinity in vitro to HLA-A*03, A*11 or B*07. Overall, 60% of the 20 peptides studied were recognized by at least one patient and 50% of the patients showed a vaccine-induced CD8+ T cell response to at least one peptide that matched their HLA specificity. We conclude that VIIR analysis is an effective strategy to directly identify immunogenic peptides that are good candidates for vaccine construction. Copyright (C) 2000 Elsevier Science B.V.
AB - With the discovery of increasing numbers of tumor antigens, there is a need to rapidly determine whether these antigens and the individual peptides they express are able to stimulate immune responses in vivo and thus, can be used to construct cancer vaccines. In this study we used the method of vaccine-induced immune response (VIIR) analysis to identify multiple immunogenic peptide epitopes derived from several melanoma associated antigens and presented by HLA-A*03, A*11 and B*07. Thirty-one patients with melanoma were immunized to a polyvalent vaccine containing multiple antigens, including MAGE-3, Melan A/MART-1, gp100 and tyrosinase. Their peripheral blood was tested for peptide-specific, vaccine-induced CD8+ T cell responses before and after immunization using an enzyme-linked immune spot (ELISPOT) assay with panels of peptides restricted by these three alleles. The peptides were selected for immunogenic potential based on their strong binding affinity in vitro to HLA-A*03, A*11 or B*07. Overall, 60% of the 20 peptides studied were recognized by at least one patient and 50% of the patients showed a vaccine-induced CD8+ T cell response to at least one peptide that matched their HLA specificity. We conclude that VIIR analysis is an effective strategy to directly identify immunogenic peptides that are good candidates for vaccine construction. Copyright (C) 2000 Elsevier Science B.V.
KW - CD8+ T cells
KW - ELISPOT
KW - Melanoma vaccine
KW - Peptide
KW - T cell epitope
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U2 - 10.1016/S0022-1759(00)00254-4
DO - 10.1016/S0022-1759(00)00254-4
M3 - Article
C2 - 11033019
AN - SCOPUS:0034692682
SN - 0022-1759
VL - 244
SP - 59
EP - 67
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
IS - 1-2
ER -