Shared human melanoma antigens: Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas

Yutaka Kawakami, Rina Zakut, Suzanne L. Topalian, Hans Stötter, Steven A. Rosenberg

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses.

Original languageEnglish
Pages (from-to)638-643
Number of pages6
JournalJournal of Immunology
Volume148
Issue number2
Publication statusPublished - 1992 Jan 15
Externally publishedYes

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Melanoma-Specific Antigens
Tumor-Infiltrating Lymphocytes
HLA-A2 Antigen
Melanoma
Cell Line
Burkitt Lymphoma
B-Cell Lymphoma
Human Herpesvirus 4

ASJC Scopus subject areas

  • Immunology

Cite this

Kawakami, Y., Zakut, R., Topalian, S. L., Stötter, H., & Rosenberg, S. A. (1992). Shared human melanoma antigens: Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. Journal of Immunology, 148(2), 638-643.

Shared human melanoma antigens : Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. / Kawakami, Yutaka; Zakut, Rina; Topalian, Suzanne L.; Stötter, Hans; Rosenberg, Steven A.

In: Journal of Immunology, Vol. 148, No. 2, 15.01.1992, p. 638-643.

Research output: Contribution to journalArticle

Kawakami, Y, Zakut, R, Topalian, SL, Stötter, H & Rosenberg, SA 1992, 'Shared human melanoma antigens: Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas', Journal of Immunology, vol. 148, no. 2, pp. 638-643.
Kawakami Y, Zakut R, Topalian SL, Stötter H, Rosenberg SA. Shared human melanoma antigens: Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. Journal of Immunology. 1992 Jan 15;148(2):638-643.
Kawakami, Yutaka ; Zakut, Rina ; Topalian, Suzanne L. ; Stötter, Hans ; Rosenberg, Steven A. / Shared human melanoma antigens : Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. In: Journal of Immunology. 1992 ; Vol. 148, No. 2. pp. 638-643.
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