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Studies on the immunogenicity of hCEA in a transgenic mouse model
Authors:M. Muders  K. Ghoreschi  M. Suckfuell  W. Zimmermann  G. Enders
Affiliation:Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Marchioninistrasse 27, 81366 Munich, Germany.
Abstract:
BACKGROUND AND AIMS: Immunization protocols in mice have shown that the tumor-associated antigen hCEA could be a target for active immunization; however, human CEA is foreign to mice. Success may depend in part on a simple anti-xenoresponse. Using hCEA-transfected syngeneic tumor cells in hCEA-transgenic mice should bypass this problem and allow testing for new vaccination strategies. MATERIALS AND METHODS: We established a hCEA transgenic model of the haplotype H2(d), which may differ from other haplotypes in cytokine production and in effectiveness of antigen presentation, and tested two vaccination protocols in wild-type and transgenic mice. RESULTS: Syngeneic wild-type mice built up an immune response with high antibody titers; only 65% of animals developed solid tumors after tumor challenge. In contrast, hCEA-transgenic mice developed no antibody response and accepted the tumor in more than 90% of cases, thus demonstrating the role of human CEA as a foreign antigen. Accordingly, active immunization using tumor lysate or lymphocytes loaded with hCEA resulted in a CTL response and tumor-rejection in up to 80% of wild-type mice. hCEA-transgenic mice could be induced with both immunization protocols to build up a CTL response, although the number of CTL were much lower and the cytotoxic response weaker than in wild-type mice. In vivo hCEA-transgenic mice rejected hCEA-positive tumors only after immunization with the tumor lysate in about 60% whereas there was no rejection of tumors after immunization with the human hCEA-loaded autologous lymphocytes. CONCLUSION: The findings clearly show the importance of transgenic models when testing the effects of immunization towards human tumor associated antigens such as hCEA because results differ in wild-type and transgenic mice.
Keywords:
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