Antigen-specific tumor vaccines: Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy

Yifan Zhai, James C. Yang, Yutaka Kawakami, Paul Spiess, Samuel C. Wadsworth, Lisa M. Cardoza, Larry A. Couture, Alan E. Smith, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved in tumor regression. In order to develop immunizing vectors for the treatment of patients with metastatic melanoma, replication-defective recombinant adenoviruses, Ad2CMV-MART1 and Ad2CMV-gp100, which encode these tumor Ags, have been generated. Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag- specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-γ, TNF-α, and granulocyte-macrophage-CSF. Sodium butyrate and TNF-α can further augment adenovirus-mediated transgene expression and increase recognition by specific CTLs. Although adenovirus- infected cells expressed the E3/19K protein at detectable levels, significant reduction of surface MHC class I expression was observed in only 3 of 10 tumor cell lines infected with either Ad2CMV-MART1 or Ad2CMV-gp100. Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally. Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect. The anti-gp100 T cells induced by Ad2CMV-gp100 vaccination appeared to be responsible for the protection. Thus, these recombinant adenoviruses encoding tumor Ags may be useful as vaccines to induce specific T cell immunity for cancer therapy.

Original languageEnglish (US)
Pages (from-to)700-710
Number of pages11
JournalJournal of Immunology
Volume156
Issue number2
StatePublished - Jan 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhai, Y., Yang, J. C., Kawakami, Y., Spiess, P., Wadsworth, S. C., Cardoza, L. M., Couture, L. A., Smith, A. E., & Rosenberg, S. A. (1996). Antigen-specific tumor vaccines: Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy. Journal of Immunology, 156(2), 700-710.