Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Front Immunol. 2021 Feb 10:11:569117. doi: 10.3389/fimmu.2020.569117. eCollection 2020.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

Keywords: CAR T-cell; access; adverse events; application; challenges; clinical strategies; relapse; resistance.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Clinical Decision-Making
  • Clinical Trials as Topic
  • Combined Modality Therapy / methods
  • Disease Management
  • Disease Susceptibility
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • Recurrence
  • Retreatment
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Receptors, Chimeric Antigen