Synthetic Antigen-Presenting Cells for Adoptive T Cell Therapy.

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. In this work, we design synthetic APCs that consist of liposomes surface-functionalized with peptide-major histocompatibility complexes (pMHC). Synthetic APCs selectively target and activate antigen-specific T cell populations to levels similar to conventional protocols using non-specific 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 could potentially be used in the future to improve the accessibility of adoptive T cell therapies by removing the need for conventional APCs during manufacturing.

• Authors: Shreyas N Dahotre, Anna M Romanov, Fang-Yi Su, Gabriel A Kwong
• Journal: Advanced therapeutics (Adv Ther (Weinh)) Vol. 4 Issue 8 (Aug 2021) ISSN: 2366-3987 [Electronic] Germany
• PMID: 34541300 (Publication Type: Journal Article)