| One of the major limitations for effective immunotherapy of cancer is central and/or peripheral tolerance by which T cells with high avidity for tumor antigens will be deleted. Only low-avidity T cells will remain available for the elimination of malignant tumor cells. The goal of this project is to optimize the activation of low-avidity T cells resulting in effective anti-tumor efficacy. Because previous data showed that CD4 help improved survival of tumor bearing mice, we intend to study the effect of CD4 cells on low-avidity CD8 cells in detail. This will be achieved by the identification of molecular characteristics that differ significantly on low-avidity T cells in the presence or absence of CD4 help. These molecules will be tested for their specific functions and their relevance in T cell activation. Molecules that might affect tumor eradication will be further analysed and tested for their effectiveness in a spontaneous tumor model. The experimental model system that is described in this proposal provides us with very useful tools to accomplish our goal. Resulting data will provide us with new possibilities to define potentially effective immunological strategies for the treatment of cancers. |
