CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities

Lionel A Kankeu Fonkoua; Olivia Sirpilla; Reona Sakemura; Elizabeth L Siegler; Saad S Kenderian

doi:10.1016/j.omto.2022.03.009

CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities

Mol Ther Oncolytics. 2022 Mar 19:25:69-77. doi: 10.1016/j.omto.2022.03.009. eCollection 2022 Jun 16.

Authors

Lionel A Kankeu Fonkoua^{1

2}, Olivia Sirpilla^{1

3

4}, Reona Sakemura^{1

5}, Elizabeth L Siegler^{1

5}, Saad S Kenderian^{1

3

5

6

7}

Affiliations

¹ T Cell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
² Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
³ Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA.
⁴ Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
⁵ Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
⁶ Department of Immunology, Mayo Clinic, Rochester, MN, USA.
⁷ Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.

Abstract

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable outcomes in individuals with hematological malignancies, but its success has been hindered by barriers intrinsic to the tumor microenvironment (TME), particularly for solid tumors, where it has yet to make its mark. In this article, we provide an updated review and future perspectives on features of the TME that represent barriers to CART cell therapy efficacy, including competition for metabolic fuels, physical barriers to infiltration, and immunosuppressive factors. We then discuss novel and promising strategies to overcome these obstacles that are in preclinical development or under clinical investigation.

Keywords: chimeric antigen receptor (CAR) T cell therapy; immunosuppression; metabolic fuels; physical barriers; tumor microenvironment.

Publication types

Review