Responses of solid tumors to chimeric antigen receptor (CAR) T cell therapy are often minimal. This is potentially due to a lack of sustained activation and proliferation of CAR T cells when encountering antigen in a profoundly immunosuppressive tumor microenvironment.
We previously demonstrated that adoptive transfer of CAR T cells in combination with a vaccine can eradicate large tumors in mice. In these studies, the extensive proliferation of CAR T cell was driven by their interaction with the major histocompatibility complex (MHC) on antigen-presenting cells (APCs), mediated by a vaccine-specific T cell receptor (TCR). However, major limitations for this approach include the need for a specific TCR and a specific vaccine for individual patients.
In the current study, we generated novel, yet safe, bispecific proteins to mediate the interaction between APCs and CAR T cells without the need for a specific TCR or vaccine. We termed these bispecifics “Bispecific Engagers of APCs and T cells (BEATs)”. Various BEAT formats have been designed; all based on an ability to simultaneously bind the CAR T cells and APCs. CAR T cell proliferation and function was enhanced by BEATs in vitro and in vivo. Both murine syngeneic and human xenograft solid tumor growth was significantly inhibited when CAR T cells were administered in combination with BEATs. This study demonstrates that facilitating the interaction of CAR T cells with APCs can enhance their antitumor activity, and the great potential of using BEATs with CAR T cells in treating solid cancers.