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[Cancer Research 62, 5058-5064, September 1, 2002]
© 2002 American Association for Cancer Research


Immunology

Identification of an Interferon-{gamma}-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 and John W. Greiner1

Laboratory of Tumor Immunology and Biology, Center for Cancer Research/National Cancer Institute, NIH, Bethesda, Maryland 20892

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-{gamma} 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-{gamma} (muIFN-{gamma}), 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-{gamma} 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-{gamma} might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 2002 by the American Association for Cancer Research.