STIMULATION OF CD8(-CELL RESPONSES TO MAGE-3 AND MELAN-A MART-1 BY IMMUNIZATION TO A POLYVALENT MELANOMA VACCINE() T)

A critical requirement for cancer vaccines is that they stimulate CD8( +) T cell responses, In this study, we tested the ability of a polyval ent melanoma vaccine to induce CD8(+) T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1, Fifteen HLA-A2(+) pati ents with resected malignant melanoma were immunized with the vaccine s.c. every 2-3 weeks, CD8(+) T cells in peripheral blood reacting to H LA-AZ restricted epitopes on MAGE-3 (FLWG-PRALV) and Melan A/MART-1/(A AGIGILTV) were quantitated using a filter spot assay at baseline and f ollowing 4 immunizations, Vaccine immunization induced CD8(+) T cells reacting to one or both of these peptides in 9 of the 15 (60%) patient s, These cells were CD8(+) and HLA-A2 restricted, as reactivity was ab rogated by monoclonal antibodies (MAbs) to CD8 and class 1 HLA, but no t by anti-CD4. All responding patients remained recurrence-free for at least 12 months (median 15 months, range 12 to >21 months), whereas m elanoma recurred within 3-5 months in non-responders, The differences in outcome were unrelated to differences in disease severity or overal l immunological competence between responders and non-responders, Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimul ate CD8(+) T cell responses in humans, and suggest that these response s are protective and surrogate markers of vaccine efficacy. (C) 1997 W iley-Liss, Inc.