Use of a single CAR T cell and several bispecific adapters facilitates eradication of multiple antigenically different solid tumors

Most solid tumors are comprised of multiple clones that express orthogonal antigens, suggesting that novel strategies must be developed in order to adapt CAR T cell therapies to treat heterogeneous solid tumors. Here we utilized a cocktail of low molecular weight bispecific adapters, each comprised of fluorescein linked to a different tumor-specific ligand, to bridge between an anti-fluorescein CAR on the engineered T cell and a unique antigen on the cancer cell. This formation of an immunological synapse between the CAR T cell and cancer cell enabled use of a single anti-fluorescein CAR T cell to eradicate a diversity of antigenically different solid tumors implanted concurrently in NSG mice. Based on these data, we suggest that a carefully designed cocktail of bispecific adapters in combination with anti-fluorescein CAR T cells can overcome tumor antigen escape mechanisms that lead to disease recurrence following many CAR T cell therapies.

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