Tumor immunotherapy using chimeric receptor redirected allogeneic T cells across MHC barriers (131.39)

Abstract

Abstract We present a strategy for adoptive immunotherapy using fully mismatched allogeneic chimeric receptor redirected T cells (allo-'T-bodies') in the absence of Graft vs. Host disease (GvHD). The strategy hinges on creating a therapeutic time-window using mild preconditioning which on one hand allows the allogeneic T-bodies enough time to effectively attack the tumor but on the other hand does not ablate the Host vs. Graft response (HvG) ensuring the eventual rejection of the allogeneic T cells thus preventing GvHD. We found that transfer of fully mismatched allogeneic T cells expressing a HER2/neu specific chimeric receptor following mild preconditioning roughly tripled the median survival of mice bearing pulmonary Renca-HER2 metastases with around 50% of mice surviving long term (>200 days) in the absence of GvHD mortality. We show that allo-T-bodies provide comparable benefit to syngeneic T-bodies, and are far superior to non-specific allogeneic T cells, demonstrating that the response is indeed tumor-specific and not merely allo-specific. Taken together these data provide proof of principle for safe and effective allogeneic adoptive therapy allowing for the use of 'universal effector cells' as a standardized treatment for cancer.