The long-term objective of this proposal is to test the hypothesis that tumor antigen (TA)-specific CTL induction combined with TA-specific monoclonal antibodies (mAb) administration enhances efficacy of immunotherapy of glioma. This hypothesis will be tested for the first time in glioma-bearing mice, taking advantage of the suitability of human high molecular weight-melanoma associated antigen (HMW-MAA) to be targeted with both cellular and humoral immunity. The proposed strategy will be tested in a mouse model utilizing the glioma TA AN2, i.e. the mouse homologue of human HMW-MAA. These proteins share >80 percent homology in their sequences.
The specific aims are to test the hypotheses that: (1) AN2-specific mAb administration, combined with AN2-specific CTL immunity induction, enhances the ability of immunotherapy to control tumor growth and prolong survival of glioma-bearing HLA-A2/Kb transgenic mice; and (2) Tumor growth control and survival prolongation are mediated by targeting of both tumor and tumor associated pericytes by AN2-specific CTL and mAb. The results generated from these studies will assess the validity for combining CTL and mAb against a novel glioma target, which is potentially useful for clinical application. ? ? ?
