Abstract:
:A critical requirement for cancer vaccines is that they stimulate CD8+ T cell responses. In this study, we tested the ability of a polyvalent melanoma vaccine to induce CD8+ T cell responses to the melanoma associated antigens MAGE-3 and Melan A/MART-1. Fifteen HLA-A2+ patients with resected malignant melanoma were immunized with the vaccine s.c. every 2-3 weeks. CD8+ T cells in peripheral blood reacting to HLA-A2 restricted epitopes on MAGE-3 (FLWGPRALV) and Melan A/MART-1/(AAGIGILTV) were quantitated using a filter spot assay at baseline and following 4 immunizations. Vaccine immunization induced CD8+ T cells reacting to one or both of these peptides in 9 of the 15 (60%) patients. These cells were CD8+ and HLA-A2 restricted, as reactivity was abrogated by monoclonal antibodies (MAbs) to CD8 and class I HLA, but not by anti-CD4. All responding patients remained recurrence-free for at least 12 months (median 15 months, range 12 to >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 responders and non-responders. Our results demonstrate directly that MAGE-3 and Melan A/MART-1 can stimulate CD8+ T cell responses in humans, and suggest that these responses are protective and surrogate markers of vaccine efficacy.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Reynolds SR,Oratz R,Shapiro RL,Hao P,Yun Z,Fotino M,Vukmanović S,Bystryn JCdoi
10.1002/(sici)1097-0215(19970917)72:6<972::aid-ijcsubject
Has Abstractpub_date
1997-09-17 00:00:00pages
972-6issue
6eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19970917)72:6<972::AID-IJCjournal_volume
72pub_type
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