Delivery of CAR-T Cells in a Transient Injectable Stimulatory Hydrogel Niche Improves Treatment of Solid Tumors

Adoptive cell therapy (ACT) has proven to be very effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. In this talk, I will describe simple-to-implement supramolecular hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. We develop Polymer-Nanoparticle hydrogels based on modified cellulose polymers and core-shell nanoparticles that interact to form an injectable hydrogel. The unique architecture of this material both simultaneously inhibits passive diffusion of entrapped cytokines, and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. We develop the formulation through novel in vitro studies and demonstrate its efficacy with cancer models in mice. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.