T-Cell Recognition of Human Melanoma Antigens

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

doi:10.1097/00002371-199308000-00002

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T-Cell Recognition of Human Melanoma Antigens

Journal article

Open access

Peer reviewed

T-Cell Recognition of Human Melanoma Antigens

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

Journal of immunotherapy with emphasis on tumor immunology, Vol.14(2), pp.88-93

08/01/1993

DOI: 10.1097/00002371-199308000-00002

PMCID: PMC2555985

PMID: 8280705

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https://www.ncbi.nlm.nih.gov/pmc/articles/2555985View

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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-A2 − melanoma and HLA-A2 + nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2 − melanomas 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 β 2 -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.

HLA-A2.1

Immunotherapy

Melanoma antigens

T-cell receptor

Tumor-infiltrating lymphocytes

Details

Title: Subtitle: T-Cell Recognition of Human Melanoma Antigens
Creators: Yutaka Kawakami - National Institutes of Health
Michael I. Nishimura - National Institutes of Health
Nicholas P. Restifo - National Institutes of Health
Suzanne L. Topalian - National Institutes of Health
Bert H. O’Neil - National Institutes of Health
Joel Shilyansky - National Institutes of Health
John R. Yannelli - National Institutes of Health
Steven A. Rosenberg - National Institutes of Health
Resource Type: Journal article
Publication Details: Journal of immunotherapy with emphasis on tumor immunology, Vol.14(2), pp.88-93
DOI: 10.1097/00002371-199308000-00002
PMID: 8280705
PMCID: PMC2555985
NLM abbreviation: J Immunother Emphasis Tumor Immunol
ISSN: 1067-5582
eISSN: 2331-3676
Language: English
Date published: 08/01/1993
Academic Unit: Stead Family Department of Pediatrics; Surgery
Record Identifier: 9984322943002771

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