2. Study of animal models to optimize cancer immunotherapy and evaluate tumor resistance mechanisms
Translation of knowledge on tumor antigens into efficient cancer immunotherapy requires additional studies on the various strategies that can be used. Some of these studies can be done in preclinical animal models. The study of such a model allowed us to uncover a powerful mechanism of tumor resistance, which is based on tryptophan catabolism by indoleamine-2,3 dioxygenase, an enzyme that we found to be frequently expressed in tumors. The resulting local tryptophan shortage appears to prevent the proliferation of lymphocytes at the tumor site. Inhibitors of indoleamine-2,3 dioxygenase can be used in vivo to counteract this tumor resistance mechanism. We are searching for new IDO inhibitors that could be developed clinically. We also study additional tumor resistance mechanisms.
The currently available murine models are limited by the fact they are based on transplantation of tumor cells grown in vitro into a healthy animal. This does not recapitulate the long-term host/tumor relationship that occurs in humans when a tumor slowly develops within a normal tissue. To circumvent this limitation and obtain more relevant information from such preclinical models, we have build a new mouse melanoma model where tumors expressing a given antigen can be induced, using a transgenic system based on Cre-lox recombination.
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