Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA

Bert H. O'Neil, Yutaka Kawakami, Nicholas P. Restifo, Jack R. Bennink, Jonathan W. Yewdell, Steven A. Rosenberg

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To detect shared human melanoma Ag that are recognized by HLA-A2 restricted, melanoma-specific CTL derived from tumor infiltrating lymphocytes, we have developed a convenient method to insert and express foreign HLA genes capable of presenting Agon target cell lines. Seventeen melanoma cell lines and 11 nonmelanoma cell lines were infected with recombinant vaccinia virus containing the HLA-A2.1 gene. Infection by the vaccinia virus resulted in expression of functional HLA-A2 molecules on the cell surface of virtually 100% of infected cells within a 3.5-h period. The results showed that 11 of 17 (65%) naturally HLA-A2- melanoma cell lines were specifically lysed by the HLA-A2-restricted, melanoma-specfic TIL after infection with the vaccinia-HLA-A2.1 virus. None of the nine human nonmelanoma cell lines tested (three colon cancer, four breast cancer, or two immortalized nontumor cell lines) or two murine melanoma cell lines were lysed by the HLA-A2-restricted TIL after vaccinia-HLA-A2.1 infection. Coinfection of the vaccinia virus containing the β2-microglobulin gene with the vaccinia-HLA-A2.1 virus increased the surface expression of HLA-A2 and subsequent lysis by melanoma-specific tumor infiltrating lymphocytes. With this new method we could extend previous findings demonstrating that shared melanoma Ag recognized by HLA-A2-restricted tumor infiltrating lymphocytes exist among melanoma cells from different patients regardless of HLA type. These Ag represent excellent candidates for the development of vaccines to induce T cell responses for the immunotherapy of patients with melanoma.

Original languageEnglish
Pages (from-to)1410-1418
Number of pages9
JournalJournal of Immunology
Volume151
Issue number3
Publication statusPublished - 1993 Aug 1
Externally publishedYes

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Melanoma-Specific Antigens
Vaccinia virus
HLA-A2 Antigen
Melanoma
Genes
Cell Line
Tumor-Infiltrating Lymphocytes
Vaccinia
Infection
Felodipine
Breast Neoplasms
Viruses
Coinfection
Immunotherapy
Colonic Neoplasms
Vaccines

ASJC Scopus subject areas

  • Immunology

Cite this

O'Neil, B. H., Kawakami, Y., Restifo, N. P., Bennink, J. R., Yewdell, J. W., & Rosenberg, S. A. (1993). Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. Journal of Immunology, 151(3), 1410-1418.

Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. / O'Neil, Bert H.; Kawakami, Yutaka; Restifo, Nicholas P.; Bennink, Jack R.; Yewdell, Jonathan W.; Rosenberg, Steven A.

In: Journal of Immunology, Vol. 151, No. 3, 01.08.1993, p. 1410-1418.

Research output: Contribution to journalArticle

O'Neil, BH, Kawakami, Y, Restifo, NP, Bennink, JR, Yewdell, JW & Rosenberg, SA 1993, 'Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA', Journal of Immunology, vol. 151, no. 3, pp. 1410-1418.
O'Neil BH, Kawakami Y, Restifo NP, Bennink JR, Yewdell JW, Rosenberg SA. Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. Journal of Immunology. 1993 Aug 1;151(3):1410-1418.
O'Neil, Bert H. ; Kawakami, Yutaka ; Restifo, Nicholas P. ; Bennink, Jack R. ; Yewdell, Jonathan W. ; Rosenberg, Steven A. / Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. In: Journal of Immunology. 1993 ; Vol. 151, No. 3. pp. 1410-1418.
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