Toward an Optimized Process for Clinical Manufacturing of CAR-Treg Cell Therapy

Chimeric antigen receptor (CAR) technology and its application to regulatory T cells (Tregs) has garnered interest among researchers in the field of cell and gene therapy. Merging the benefits of CAR technology with Tregs offers a novel and promising therapeutic option for durable reshaping of undesired immune responses following solid organ or hematopoietic stem cell transplantation, as well as in immune-related disorders. However, major challenges remain for developing a standardized and robust good manufacturing practice (GMP)-compliant manufacturing process for CAR-Treg cells. We review current progress in the field and recommend ways to improve CAR-Treg manufacturing processes based on lessons learned from first-generation Treg therapeutics as well as from anticancer CAR-T cell development. Advances in the field of cell therapy have led to promising novel approaches to treat malignancies and other debilitating diseases. Redirecting the target antigen specificity of CAR-Treg cells represents one such promising approach.The clinical success of anticancer CAR-T cells will, in all likelihood, accelerate the clinical translation of CAR-Treg therapeutics aimed at reshaping undesired immune responses following solid organ or hematopoietic stem cell transplantation as well as in immune-related disorders.Current manufacturing processes for CAR-Tregs demonstrate challenges in cell purification, yield, expansion, CAR selection and gene delivery, supply chain, and quality control/product release testing.We propose a GMP-compatible manufacturing framework to enhance the CAR-Treg production process for clinical application.