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Vaccine-induced CD8+ T-cell Responses to MAGE-3 Correlate with Clinical Outcome in Patients with Melanoma¹

Departments of Dermatology [S. R. R., D. J., J-C. B.], Environmental Medicine [A. Z-J.], Surgery [R. L. S., D. F. R., M. N. H.], New York University School of Medicine, Kaplan Comprehensive Cancer Center, and Hunter College School of Health Sciences [D. J.], New York, New York 10016

Purpose: Vaccine-induced antitumor CD8+ T-cell responses are believed to play an important role in increasing resistance to melanoma. The following study was conducted to examine whether these responses are associated with improved clinical outcome in melanoma vaccine-treated patients.

Experimental Design: We measured CD8+ T-cell responses to gp100, MART-1, MAGE-3, and tyrosinase by enzyme-linked immunospot assay in peripheral blood of 131 HLA-A*01- or HLA-A*02-positive melanoma patients before and after immunization to a polyvalent, shed antigen, melanoma vaccine, and correlated the results with clinical outcome.

Results: Fifty-six percent of patients had a vaccine-induced CD8+ T-cell response to at least one of the four antigens. Recurrences were significantly reduced in patients with vaccine-induced responses to MAGE-3 (hazard ratio, 0.42; 95% confidence interval, 0.18–0.99; P = 0.03) by the Cox proportional hazard model but were unrelated to responses to the other three antigens. Patients with a preexisting response to any of the four antigens were significantly more likely to have a further vaccine-boosted response to that same antigen (P < 0.0001–0.036).

Conclusions: There was a correlation between vaccine-induced CD8+ T-cell responses to melanoma-associated antigens and improved clinical outcome, but the correlation depended on the antigen against which the response is directed. The only significant correlation was with responses to MAGE-3.

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