Design and Fabrication of Biodegradable TSP for Therapeutic Compound and CAR T Cell Delivery

CAR T cell therapy reliably results in positive effect on patients with hematologic malignancy but shows less efficacy in solid tumor treatments due to limited trafficking and tumor infiltration, intensive CAR T-related toxicities and antigen scape. So, a cell delivery platform is required to overcome these limitations and improve efficacy towards solid tumor treatments. Here, we have introduced a biodegradable implantable polymeric cell delivery device that delivers CAR T cells to tumor site in a prolong and sustained manner. These milliammeter-size GelMA toroidal spiral particles (TSPs) presenting an internal void volume for high-capacity cell loading, are used as a co-delivery system of MSLN CAR T cell and IL-2, a growth factor essential for cell expansion and proliferation. A sustained cytokine and cell release out of these particles has achieved while maintaining a high cell proliferation and viability in vitro. In a NSG mouse model of breast cancer and colorectal carcinoma, we found that CAR T cells can successfully migrate from these particles to the solid tumor and control tumor outgrowth more effectively than systemic and peri-tumoral administration of CAR T cells. So, biodegradable GelMA TSPs may improve anti-tumor efficacy of CAR T cell therapy for solid tumor treatment.