Scalable Manufacturing of CAR T cells for Cancer Immunotherapy

Blood Cancer Discov. 2021 Sep;2(5):408-422. doi: 10.1158/2643-3230.BCD-21-0084. Epub 2021 Aug 3.

Abstract

As of April 2021, there are five commercially available chimeric antigen receptor (CAR) T cell therapies for hematological malignancies. With the current transition of CAR T cell manufacturing from academia to industry, there is a shift toward Good Manufacturing Practice (GMP)-compliant closed and automated systems to ensure reproducibility and to meet the increased demand for cancer patients. In this review we describe current CAR T cells clinical manufacturing models and discuss emerging technological advances that embrace scaling and production optimization. We summarize measures being used to shorten CAR T-cell manufacturing times and highlight regulatory challenges to scaling production for clinical use.

Statement of significance ∣: As the demand for CAR T cell cancer therapy increases, several closed and automated production platforms are being deployed, and others are in development.This review provides a critical appraisal of these technologies that can be leveraged to scale and optimize the production of next generation CAR T cells.

Keywords: Automation; CAR T cells; Clinical Production; GMP; Genetic Modification; Hematological Malignancies; Manufacturing; Scaling; Solid Tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunotherapy, Adoptive*
  • Neoplasms* / therapy
  • Reproducibility of Results
  • T-Lymphocytes