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Proof of concept and mode of action of a novel modular platform for adoptive T cell therapy combining bispecific antibodies with synthetic agonistic receptors

      Background: In adoptive T cell therapy (ACT), one of the greatest challenges is the recruitment of T cells to tumor tissue. T cells, engineered with chimeric antigen receptors (CAR) haven proven efficacy for hematological malignancies but at the same time induce severe side effects such as cytokine release syndrome. We herein describe a novel MHC-unrestricted modular platform by combining autologous T cells, transduced with a targetable synthetic agonistic receptor (SAR), with crosslinking bispecific antibodies (BiAb) that specifically recruit and activate T cells to the tumor tissue.
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