Synthetic Antigen‐Presenting Cells for Adoptive T Cell Therapy
Shreyas N. Dahotre, Anna Romanov, Fang‐Yi Su, Gabriel A. Kwong
Abstract
Abstract Adoptive T cell therapies are transforming the treatment of solid and liquid tumors, yet their widespread adoption is limited in part by the challenge of generating functional cells. T cell activation and expansion using conventional antigen‐presenting cells (APCs) is unreliable due to the variable quality of donor‐derived APCs. As a result, engineered approaches using nanomaterials presenting T cell activation signals are a promising alternative due to their ability to be robustly manufactured with precise control over stimulation cues. Here, synthetic APCs that consist of liposomes surface‐functionalized with peptide‐major histocompatibility complexes are designed. Synthetic APCs selectively target and activate antigen‐specific T cell populations to levels similar to conventional protocols using nonspecific αCD3 and αCD28 antibodies without the need for costimulation signals. T cells treated with synthetic APCs produce effector cytokines and demonstrate cytotoxic activity when co‐cultured with tumor cells presenting target antigen in vitro. Following adoptive transfer into tumor‐bearing mice, activated cells control tumor growth and improve overall survival compared to untreated mice. Synthetic APCs can potentially be used in the future to improve the accessibility of adoptive T cell therapies by removing the need for conventional APCs during manufacturing.