Through the membrane-insertion properties of amphiphilic CAR-ligands, we demonstrate in vivo expansion of CAR T cells while simultaneously decorating the surface of tumor cells for CAR T trafficking.

While CAR T cell therapy has been successful in treating many blood cancers, we have yet to see a clinical translation of that success in patients with solid tumors. There are numerous culprits which lay roadblocks for researchers and clinicians working with solid tumors including antigen heterogeneity, tumor trafficking and infiltration, and a highly immunosuppressive tumor microenvironment. To overcome some of these challenges, we developed a method to vaccine boost CAR T cells using an amphiphilic CAR ligand that drains directly to lymph nodes following a subcutaneous injection for CAR T cell stimulation and massive expansion. The boosted CAR T cells, bolstered in number and function, subsequently induce spreading of neoantigens upon initial tumor cell death which primes endogenous T cells to further inflame the tumor by targeting displayed neoepitopes. We further utilized the amph-ligand to decorate solid tumors, effectively creating a tumor-agnostic CAR T cell therapy for solid tissue cancers.