Immunisierung gegen das Tumorantigen CEA: Vergleichende Untersuchung an Wildtyp- und CEA transgenen Mäusen

Immunization protocols in animal models have shown that the tumor-associated antigen CEA could be a target for active immunization. Since human CEA which does not exist in the rodent genome has been used in these models it is hard to decide whether part of the immune response is directed only to the foreign antigen (anti-allo). We established an animal model on H2d background using CEA transfected tumor cells and CEA transgenic mice. Transplanting CEA transfected cells s.c. in wild type mice clearly shows, that the animals build up an immune response with high antibody titers in serum. Accordingly, only 55% of the animals developed solid tumors after tumor challenge. A cellular immune response could not be detected. In contrast, CEA transgenic mice did not develop any immune response and accepted the tumor in 90 % thus demonstrating the role of the foreign antigen. Active immunization using tumor lysates or lymphocytes loaded with human CEA was able to induce a CTL response as well as tumor-rejection in up to 76% of wild type mice. The immune response after intraperitoneal tumor lysate vaccination was not CEA specific and was able to lyse non-transfected CEA negative wild type tumor cells as well. CEA-transgenic mice could be induced to build up a CTL response in vitro with both vaccination protocols. In vivo CEA-transgenic mice rejected CEA-positive tumors in about 60% after immunization with the tumor lysate but not after intravenous vaccination with the CEA-loaded autologous lymphocytes. As there was a big difference in the reaction of the immune response to CEA between wild-type and transgenic rodents, the experiments clearly show the importance of transgenic models when testing the effects of immunization towards human tumor associated antigens. The induction of cross-priming with antigens other than CEA or the use of (co)stimulatory molecules must be taken into account when using CEA in vector systems for immunization.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2003

Author dc:creator

• Muders, Michael H.

Repository record source_url

https://edoc.ub.uni-muenchen.de/737/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:737