The use of melanosomal proteins in the immunotherapy of melanoma

Yutaka Kawakami, Paul F. Robbins, Rong Fu Wang, Maria Parkhurst, Xiaoqiang Kang, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Clinical observations in the interleukin (IL) 2-based immunotherapies suggest that T cells play a central role in the rejection of melanoma. Using cDNA expression cloning, we have isolated genes encoding melanoma antigens recognized by tumor-infiltrating T lymphocytes. These antigens are categorized as (a) melanocyte-specific melanosomal proteins (MART-1/melan A, gp100, tyrosinase, TRP-1, and TRP-2), (b) tumor-specific mutated proteins (β-catenin), and (c) others (p15). A variety of mechanisms has been identified for the generation of T cell epitopes on tumor cells. Some of the HLA-A2 binding epitopes from the melanosomal antigens appear to be subdominant self-determinants with relatively low major histocompatibility complex binding affinity. The effectiveness of adoptive transfer into patients of cytotoxic T lymphocytes recognizing the melanosomal antigens, the significant correlation between vitiligo development and clinical response in patients receiving IL-2-based immunotherapies, and the sporadic tumor regressions observed in some patients following immunization with the MART-1 or gp100 peptides in incomplete Freund’s adjuvant or recombinant viruses expressing the MART-1 antigen suggest that these epitopes may represent tumor rejection antigens. Phase I immunization trials using peptides or recombinant viruses containing genes encoding the melanosomal antigens MART-1 or gp100, with or without co-administration of cytokines such as IL-2, IL-12, or granulocyte-macrophage colony-stimulating factor, are being conducted in the Surgery Branch of the National Cancer Institute. These studies may demonstrate the feasibility of using melanosomal proteins for the immunotherapy of patients with melanoma.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalJournal of Immunotherapy
Volume21
Issue number4
DOIs
StatePublished - Jan 1 1998

    Fingerprint

Keywords

  • GP100
  • Immunotherapy
  • MART-1
  • Melanoma antigens
  • Subdominant epitopes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Kawakami, Y., Robbins, P. F., Wang, R. F., Parkhurst, M., Kang, X., & Rosenberg, S. A. (1998). The use of melanosomal proteins in the immunotherapy of melanoma. Journal of Immunotherapy, 21(4), 237-246. https://doi.org/10.1097/00002371-199807000-00001