Engineering metabolism of chimeric antigen receptor (Car) cells for developing efficient immunotherapies

Joslyn L. Mangal, Jamie L. Handlos, Arezoo Esrafili, Sahil Inamdar, Sidnee McMillian, Mamta Wankhede, Riccardo Gottardi, Abhinav P. Acharya

Research output: Contribution to journalReview articlepeer-review

Abstract

Chimeric antigen receptor (CAR) T cell‐based therapies have shown tremendous advance-ment in clinical and pre‐clinical studies for the treatment of hematological malignancies, such as the refractory of pre‐B cell acute lymphoblastic leukemia (B‐ALL), chronic lymphocytic leukemia (CLL), and large B cell lymphoma (LBCL). However, CAR T cell therapy for solid tumors has not been successful clinically. Although, some research efforts, such as combining CARs with immune checkpoint inhibitor‐based therapy, have been used to expand the application of CAR T cells for the treatment of solid tumors. Importantly, further understanding of the coordination of nutrient and energy supplies needed for CAR T cell expansion and function, especially in the tumor microenvironment (TME), is greatly needed. In addition to CAR T cells, there is great interest in utilizing other types of CAR immune cells, such as CAR NK and CAR macrophages that can infiltrate solid tumors. However, the metabolic competition in the TME between cancer cells and immune cells remains a challenge. Bioengineering technologies, such as metabolic engineering, can make a substantial con-tribution when developing CAR cells to have an ability to overcome nutrient‐paucity in the solid TME. This review introduces technologies that have been used to generate metabolically fit CAR-immune cells as a treatment for hematological malignancies and solid tumors, and briefly discusses the challenges to treat solid tumors with CAR‐immune cells.

Original languageEnglish (US)
Article number1123
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2021

Keywords

  • CAR T cell
  • CAR macrophage
  • Immunometabolism
  • Immunotherapy
  • Solid tumors
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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