Induction of protective host immunity to carcinoembryonic antigen (CEA), aself-antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus

Human carcinoembryonic antigen (CEA is a well-characterized oncofetal glyco protein whose overexpression by human carcinomas has been a target for canc er immunotherapy, Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This st udy investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mic e to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unr esponsive to CEA, as shown by the lack of detectable CEA-specific serum ant ibodies and the inability to prime an in vitro splenic T-cell response to C EA. Furthermore, the administration of whole CEA protein in adjuvant to CEA .Tg mice failed to elicit either anti-CEA Ige titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers a ere round in those mic e. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expre ssing CEA generated relatively strong anti-CEA Ige antibody titers and demo nstrated evidence of immunoglobulin class switching, These mice also develo ped T(H)1-type CEA-specific CD4(+) responses and CEA peptide-specific cytot oxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA,Tg mice against a challenge with CEA-expressing tumo r cells, Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissues. The results demons trate the ability to generate an effective antitumor immune response to a t umor self-antigen by immunization with a recombinant vaccinia virus. CEA,Tg mice should be an excellent experimental model to study the effects of mor e aggressive immunization schemes directed at established tumors with the p ossible development of accompanying autoimmune responses involving normal t issues.