A polyvalent melanoma vaccine induces MAGE-3 and MART-1/Melan-A specific CD8+ T cell responses that correlate with clinical outcome (Meeting abstract).

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

A polyvalent melanoma vaccine induces MAGE-3 and MART-1/Melan-A specific CD8+ T cell responses that correlate with clinical outcome (Meeting abstract).

Proc Annu Meet Am Soc Clin Oncol; 16:A1548 1997. Unique Identifier : AIDSLINE ICDB/98643548
Oratz R; Reynolds SR; Shapiro RL; Harris M; Roses D; Vukmanovic S; Bystryn JC; Depts. of Medicine, Dermatology, Surgery and Pathology, Kaplan; Cancer Center, NYU Medical Center, NY, NY 10016

Abstract: A critical requirement to use tumor antigens as vaccines is that they stimulate CD8+ T cell responses. In this study, we tested the ability of a shed, polyvalent, melanoma antigen vaccine to induce such responses to the melanoma-associated antigens, MAGE-3 and MART-1/Melan-A. Fifteen HLA-A2+ patients with resected malignant melanoma were immunized to the vaccine sc every 2-3 weeks x 4, and monthly thereafter. CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and/or MART-1/Melan-A (AAGIGILTV) were quantitated directly using a filter spot assay at baseline and following 4 immunizations. Vaccine immunization induced CD8+ T cells reacting specifically to one or both of these antigens in 9 (60%) patients. These cells were CD8+ and HLA-A2 restricted, as reactivity was abrogated by monoclonal antibodies to CD8 and to class I HLA, but not by anti-CD4. The CD8+ T cells were specifically directed to these antigens, as they did not react to the same targets pulsed with a control HLA-A2 restricted peptide recognized by T cells. All responding patients remained recurrence-free during a follow-up of 12-21 months, whereas melanoma recurred within 3-5 months in non-responders. The differences in outcome were unrelated to differences in disease-severity or overall immunological competence between CD8+ T cell responders and non-responders. These results demonstrate that a polyvalent vaccine can stimulate a CD8+ T cell response to MAGE-3 and MART-1/Melan-A in humans, and suggest that the responses are protective and surrogate markers of vaccine efficacy.

Keywords: CD8-Positive T-Lymphocytes/*IMMUNOLOGY Cancer Vaccines/*THERAPEUTIC USE Cross Reactions HLA-A2 Antigen/IMMUNOLOGY Human Melanoma/IMMUNOLOGY/*THERAPY Neoplasm Proteins/*IMMUNOLOGY Treatment Outcome ABSTRACT
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M9820748

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