Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
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 CEA(526-533) 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-2D(b)-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.
Laboratory of Tumor Immunology and Biology, Center for Cancer Research/National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
John
J
Schmitz
Eva
E
Reali
James W
JW
Hodge
Arti
A
Patel
Garland
G
Davis
Jeffrey
J
Schlom
John W
JW
Greiner
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D002272:Carcinoembryonic Antigen; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma