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

74 Citations (Scopus)

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
Pages (from-to)237-246
Number of pages10
JournalJournal of Immunotherapy
Volume21
Issue number4
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

MART-1 Antigen
Immunotherapy
Melanoma
Interleukin-2
Antigens
Epitopes
Immunization
Proteins
Melanoma-Specific Antigens
Viruses
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
HLA-A2 Antigen
Catenins
Neoplasms
Vitiligo
Peptides
T-Lymphocyte Epitopes
Monophenol Monooxygenase
National Cancer Institute (U.S.)

Keywords

  • gp100
  • Immunotherapy
  • MART-1
  • Melanoma antigens
  • Subdominant epitopes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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.

The use of melanosomal proteins in the immunotherapy of melanoma. / Kawakami, Yutaka; Robbins, Paul F.; Wang, Rong Fu; Parkhurst, Maria; Kang, Xiaoqiang; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 21, No. 4, 1998, p. 237-246.

Research output: Contribution to journalArticle

Kawakami, Y, Robbins, PF, Wang, RF, Parkhurst, M, Kang, X & Rosenberg, SA 1998, 'The use of melanosomal proteins in the immunotherapy of melanoma', Journal of Immunotherapy, vol. 21, no. 4, pp. 237-246.
Kawakami Y, Robbins PF, Wang RF, Parkhurst M, Kang X, Rosenberg SA. The use of melanosomal proteins in the immunotherapy of melanoma. Journal of Immunotherapy. 1998;21(4):237-246.
Kawakami, Yutaka ; Robbins, Paul F. ; Wang, Rong Fu ; Parkhurst, Maria ; Kang, Xiaoqiang ; Rosenberg, Steven A. / The use of melanosomal proteins in the immunotherapy of melanoma. In: Journal of Immunotherapy. 1998 ; Vol. 21, No. 4. pp. 237-246.
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