Despite the remarkable clinical efficacy of chimeric antigen receptor (CAR) T cells in hematological malignancies, only a subset of patients achieve a durable complete response (dCR). DCR has been correlated with CAR T cell products enriched with T cells of memory phenotypes. Therefore, reagents that consistently promote memory phenotypes during the manufacturing of CAR T cell products have the potential to significantly improve clinical outcomes. We have developed a novel modular multi-cytokine particle (MCP) platform 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 assembly and screening of compositionally diverse MCP libraries to identify formulations tailored to promote specific phenotypes with a high degree of flexibility. We leveraged this platform to identify unique MCP formulations that increase the proportion of memory phenotype CAR T cells. MCP-manufactured CAR T cell products exhibit increased proportions of memory-like phenotypes in diffuse large B cell lymphoma (DLBCL) patient CAR T cells and demonstrate superior anti-tumor efficacy in mouse models of lymphoma and ovarian cancer through enhanced persistence. Our 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. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
