Induction of tumor-reactive CTL from peripheral blood and tumor- infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1

L. Rivoltini, Y. Kawakami, K. Sakaguchi, S. Southwood, A. Sette, P. F. Robbins, F. M. Marincola, M. L. Salgaller, J. R. Yannelli, E. Appella, S. A. Rosenberg

Research output: Contribution to journalArticle

299 Citations (Scopus)

Abstract

MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-127-35 peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-135-43-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-127-35-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA- A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-127-35 peptide. These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-127-35, as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-127-35 also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-127-35 mediated 25- to 100- fold higher lytic activity than MART-1-reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-127-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

Original languageEnglish
Pages (from-to)2257-2265
Number of pages9
JournalJournal of Immunology
Volume154
Issue number5
Publication statusPublished - 1995 Jan 1

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rivoltini, L., Kawakami, Y., Sakaguchi, K., Southwood, S., Sette, A., Robbins, P. F., Marincola, F. M., Salgaller, M. L., Yannelli, J. R., Appella, E., & Rosenberg, S. A. (1995). Induction of tumor-reactive CTL from peripheral blood and tumor- infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. Journal of Immunology, 154(5), 2257-2265.