Manufacturing chimeric antigen receptor T cells: issues and challenges

Cytotherapy. 2019 Mar;21(3):327-340. doi: 10.1016/j.jcyt.2018.11.009. Epub 2019 Jan 23.

Abstract

Clinical trials of adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have delivered unprecedented responses in patients with relapsed refractory B-cell malignancy. These results have prompted Food and Drug Administration (FDA) approval of two CAR T-cell products in this high-risk patient population. The widening range of indications for CAR T-cell therapy and increasing patient numbers present a significant logistical challenge to manufacturers aiming for reproducible delivery systems for high-quality clinical CAR T-cell products. This review discusses current and novel CAR T-cell processing methodologies and the quality control systems needed to meet the increasing clinical demand for these exciting new therapies.

Keywords: CliniMACS Prodigy; chimeric antigen receptor T cells; immunotherapy; lentiviral vectors.

Publication types

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

MeSH terms

  • Antigens, CD19 / immunology
  • Blood Component Removal / methods
  • Cell Survival
  • Cryopreservation / methods
  • Endotoxins / analysis
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation
  • Manufacturing and Industrial Facilities / standards*
  • Mycoplasma
  • Neoplasms / therapy*
  • Quality Control*
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes / immunology
  • Transduction, Genetic / methods

Substances

  • Antigens, CD19
  • Endotoxins
  • Receptors, Chimeric Antigen