Human melanoma antigens recognized by T lymphocytes

Yutaka Kawakami, Paul F. Robbins, Steven A. Rosenberg

Research output: Contribution to journalReview article

Abstract

Human melanoma antigens and their epitopes recognized by T cells have been identified using a variety of methods. These antigens are classified as 1) melanocyte specific melanosomal proteins (MART-1, gp100, tyrosinase and TRP-1), 2) proteins expressed in testis and a variety of cancers (MAGE-1, MAGE-3, BAGE and GAGE), 3) tumor specific mutated proteins (β-catenin, MUM-1 and CDK4), and 4) others (p15). Some of the HLA-A2 binding non-mutated melanoma epitopes contained non-dominant anchor amino acids and have relatively low HLA-A2 binding affinity, suggesting that these epitopes were likely to be subdominant or cryptic self determinants. The significant correlation observed between vitiligo development and IL2 based immunotherapy suggested that autoreactive T cells specific for these self peptides were involved in melanoma regression in vivo. In addition, since adoptive transfer into patients of CTL recognizing these epitopes resulted in tumor regression, these epitopes may be tumor rejection antigens. Melanoma reactive CTL were efficiently induced from PBL of patients by in vitro stimulation wilh PBMC pulsed with these melanoma epitopes and may be useful in adoptive transfer protocols for the treatment of patients with metastatic melanoma. An immunization trial using the MART-1 and gp100 peptides in conjunction with incomplete Freund's adjuvant is in progress. These identified antigens may be useful for the development of new immunotherapies for the treatment of melanoma patients as well as for understanding the mechanisms of anti-tumor immune responses and autoimmune disorders against melanocytes.

Original languageEnglish (US)
Pages (from-to)100-108
Number of pages9
JournalKeio Journal of Medicine
Volume45
Issue number2
DOIs
StatePublished - Jun 1996

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Keywords

  • MHC class I
  • T cells
  • cryptic self determinants
  • immunotherapy
  • tumor antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kawakami, Y., Robbins, P. F., & Rosenberg, S. A. (1996). Human melanoma antigens recognized by T lymphocytes. Keio Journal of Medicine, 45(2), 100-108. https://doi.org/10.2302/kjm.45.100