Engineering Improved CAR T Cell Products with A Multi‐Cytokine Particle Platform for Hematologic and Solid Tumors

Despite the remarkable clinical efficacy of chimeric antigen receptor (CAR) T cells in hematological malignancies, only a subset of patients achieves a durable complete response (dCR). DCR has been correlated with CAR T cell products enriched with T cells memory phenotypes. Therefore, reagents that consistently promote memory phenotypes during the manufacturing of CAR T cells have the potential to significantly improve clinical outcomes. A novel modular multi‐cytokine particle (MCP) platform is developed that combines the signals necessary for activation, costimulation, and cytokine support into a single “all‐in‐one” stimulation reagent for CAR T cell manufacturing. This platform allows for the assembly and screening of compositionally diverse MCP libraries to identify formulations tailored to promote specific phenotypes with a high degree of flexibility. The approach is leveraged to identify unique MCP formulations that manufacture CAR T cell products from diffuse large B cell patients with increased proportions of memory‐like phenotypes MCP‐manufactured CAR T cells demonstrate superior anti‐tumor efficacy in mouse models of lymphoma and ovarian cancer through enhanced persistence. These findings serve as a proof‐of‐principle of the powerful utility of the MCP platform to identify “all‐in‐one” stimulation reagents that can improve the effectiveness of cell therapy products through optimal manufacturing. The multi‐cytokine particle (MCP) platform combines the signals necessary for T cell activation, costimulation, and cytokine support into a single “all‐in‐one” reagent that can improve the effectiveness of cell therapy products through optimal manufacturing. MCP‐manufactured CAR T cell products exhibit increased proportions of memory‐like phenotypes and demonstrate superior anti‐tumor efficacy in mouse models of lymphoma and ovarian cancer.