T-Cell recognition of human melanoma antigens

Yutaka Kawakami, Michael I. Nishimura, Nicholas P. Restifo, Suzanne Topalian, Bert H. O'Neil, Joel Shilyansky, John R. Yannelli, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) has antitumor activity in some patients with metastatic melanoma. We have analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured TILs specifically lysed autologous and some allogeneic melanomas sharing a variety of class I major histocompatibility complex (MHC) molecules. HLA-A2—restricted melanoma-specific TILs lysed many HLA-A2+melanoma cell lines from different patients but failed to lyse HLA-A2melanoma and HLA-A2+nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These results indicate that shared melanoma antigens (Ag) are expressed in melanomas regardless of their human leukocyte antigen types. In order to identify these shared melanoma Ags, we have tested some known proteins expressed in melanoma. Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also attempting to isolate antigenic peptides by high performance liquid chromatography separation and genes encoding melanoma Ag by cDNA expression cloning. The T-cell component of the antimelanoma response was also analyzed by determining the genetic structure of the T-cell receptor (TCR) used by melanoma TILs. However, we did not observe common TCR variable region usage by different melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL lysis due to the absence of or defects in the expression of Ag, MHC, or β2-microglobulin molecules. These data indicate multiple mechanisms for melanoma escape from T-cell immunosurveillance. These findings have important implications for the development of immunotherapies for melanoma.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
JournalJournal of Immunotherapy
Volume14
Issue number2
StatePublished - 1993
Externally publishedYes

Fingerprint

Melanoma-Specific Antigens
Tumor-Infiltrating Lymphocytes
Melanoma
T-Lymphocytes
HLA-A2 Antigen
T-Cell Antigen Receptor
Major Histocompatibility Complex
Cell Line
Antigens
Immunologic Monitoring
Monophenol Monooxygenase
Adoptive Transfer
Vaccinia virus
Genetic Structures
Cellular Structures
HLA Antigens
Immunotherapy
Genes
Interleukin-2

Keywords

  • HLA-A2.1
  • Immunotherapy
  • Melanoma antigens
  • T-cell receptor
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Kawakami, Y., Nishimura, M. I., Restifo, N. P., Topalian, S., O'Neil, B. H., Shilyansky, J., ... Rosenberg, S. A. (1993). T-Cell recognition of human melanoma antigens. Journal of Immunotherapy, 14(2), 88-93.

T-Cell recognition of human melanoma antigens. / Kawakami, Yutaka; Nishimura, Michael I.; Restifo, Nicholas P.; Topalian, Suzanne; O'Neil, Bert H.; Shilyansky, Joel; Yannelli, John R.; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 14, No. 2, 1993, p. 88-93.

Research output: Contribution to journalArticle

Kawakami, Y, Nishimura, MI, Restifo, NP, Topalian, S, O'Neil, BH, Shilyansky, J, Yannelli, JR & Rosenberg, SA 1993, 'T-Cell recognition of human melanoma antigens', Journal of Immunotherapy, vol. 14, no. 2, pp. 88-93.
Kawakami Y, Nishimura MI, Restifo NP, Topalian S, O'Neil BH, Shilyansky J et al. T-Cell recognition of human melanoma antigens. Journal of Immunotherapy. 1993;14(2):88-93.
Kawakami, Yutaka ; Nishimura, Michael I. ; Restifo, Nicholas P. ; Topalian, Suzanne ; O'Neil, Bert H. ; Shilyansky, Joel ; Yannelli, John R. ; Rosenberg, Steven A. / T-Cell recognition of human melanoma antigens. In: Journal of Immunotherapy. 1993 ; Vol. 14, No. 2. pp. 88-93.
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