Identification of an interferon-γ-inducible carcinoembryonic antigen (CEA) CD8+ T-cell epitope, which mediates tumor killing in CEA transgenic mice

John Schmitz, Eva Reali, James W. Hodge, Arti Patel, Garland Davis, Jeffrey Schlom, John W. Greiner

Research output: Contribution to journalArticle

Abstract

This study describes a CD8+ T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine. Incubation of splenocytes from the immune CEA.Tg mice with the CEA526-533 peptide resulted in the outgrowth of low-avidity CD8+ T cells, which produced IFN-γ and mediated perforin-dependent tumor cell lysis. However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-γ (muIFN-γ), and lysis was H-2Db- restricted and involved the Fas-FasL-mediated cytotoxic pathway. When the CEA peptide-specific T cells were used as in vivo effectors in adoptive T-cell transfer studies, muIFN-γ treatment of the CEA.Tg mice was again required for T-cell-dependent growth suppression of CEA-expressing metastatic tumors. The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-γ might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.

Original languageEnglish
Pages (from-to)5058-5064
Number of pages7
JournalCancer Research
Volume62
Issue number17
Publication statusPublished - Sep 1 2002

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Schmitz, J., Reali, E., Hodge, J. W., Patel, A., Davis, G., Schlom, J., & Greiner, J. W. (2002). Identification of an interferon-γ-inducible carcinoembryonic antigen (CEA) CD8+ T-cell epitope, which mediates tumor killing in CEA transgenic mice. Cancer Research, 62(17), 5058-5064.