CAR-T Cell Therapies: An Overview of Clinical Studies Supporting Their Approved Use against Acute Lymphoblastic Leukemia and Large B-Cell Lymphomas

Int J Mol Sci. 2020 May 30;21(11):3906. doi: 10.3390/ijms21113906.

Abstract

Chimeric Antigen Receptor (CAR)-T cell therapy is an exciting development in the field of cancer immunology, wherein immune T-cells from patients are collected, engineered to create 'CAR'-T cells, and infused back into the same patient. Currently, two CAR-T-cell-based therapies, Tisagenlecleucel and Axicabtagene ciloleucel, are approved by FDA for the treatment of hematological malignancies, acute lymphoblastic leukemia and large B-cell lymphomas. Their approval has been a culmination of several phase I and II clinical studies, which are the subject of discussion in this review article. Over the years, CAR-T cells have evolved to be significantly more persistent in patients' blood, resulting in a much-improved clinical response and disease remission. This is particularly significant given that the target patient populations of these therapies are those with relapsed and refractory disease who have often progressed on multiple therapies. Despite the promising clinical results, there are still several challenges that need to be addressed. Of particular note are the associated toxicities exemplified by cytokine release syndrome (CRS) and the neurotoxicity. CRS has been addressed by an FDA-approved therapy of its own-tocilizumab. This article focuses on the progress related to CAR-T therapy: the pertinent clinical studies and their major findings, their associated adverse effects, and future perspective.

Keywords: CAR-T cell therapy; axicabtagene ciloleucel; cytokine release syndrome; tisagenlecleucel; tocilizumab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD19 / therapeutic use
  • Biological Products
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Drug Approval*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, B-Cell / therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / therapeutic use
  • Remission Induction

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD19
  • Biological Products
  • Cytokines
  • Receptors, Antigen, T-Cell
  • tocilizumab
  • tisagenlecleucel
  • axicabtagene ciloleucel