Immunisierung gegen das Tumorantigen CEA: Vergleichende Untersuchung an Wildtyp- und CEA transgenen Mäusen
Beschreibung
vor 21 Jahren
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.
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.
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