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

Trends Biotechnol. 2020 Oct;38(10):1099-1112. doi: 10.1016/j.tibtech.2019.12.009. Epub 2020 Jan 22.

Abstract

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.

Keywords: CAR-T; CAR-Tregs; GMP manufacturing; automation; clinical development; closed systems; gene editing; hematopoietic stem cell transplantation; immunosuppression; regulatory T cells; solid organ transplantation; tolerance induction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bioreactors*
  • Cell Culture Techniques*
  • Cell Engineering*
  • Genetic Therapy
  • Humans
  • Immunotherapy, Adoptive*
  • Mice
  • T-Lymphocytes, Regulatory* / chemistry
  • T-Lymphocytes, Regulatory* / cytology
  • T-Lymphocytes, Regulatory* / metabolism