Next-generation CAR T cells to overcome current drawbacks

Int J Hematol. 2021 Nov;114(5):532-543. doi: 10.1007/s12185-020-02923-9. Epub 2020 Jun 27.

Abstract

As a rapidly emerging treatment in the oncology field, adoptive transfer of autologous, genetically modified chimeric antigen receptor (CAR) T cells has shown striking efficacy and is curative in certain relapsed/refractory patients with hematologic malignancy. This treatment modality of using a "living drug" offers many tantalizing and novel therapeutic strategies for cancer patients whose remaining treatment options may have otherwise been limited. Despite the early success of CAR T cells in hematologic malignancies, many barriers remain for widespread adoption. General barriers include cellular manufacturing limitations, baseline quality of the T cells, adverse events post-infusion such as cytokine release syndrome (CRS) and neurotoxicity, and host rejection of non-human CARs. Additionally, each hematologic disease presents unique mechanisms of relapse which have to be addressed in future clinical trials if we are to augment the efficacy of CAR T treatment. In this review, we will describe current barriers to hindering efficacy of CAR T-cell treatment for hematologic malignancies in a disease-specific manner and review recent innovations aimed at enhancing the potency and applicability of CAR T cells, with the overall goal of building a framework to begin incorporating this form of therapy into the standard medical management of blood cancers.

Keywords: CAR T cell; Cancer; Chimeric antigen receptor; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Disease Management
  • Disease Susceptibility
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / economics
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / trends
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Prognosis
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Treatment Outcome

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen