Understanding CAR T cell-tumor interactions: Paving the way for successful clinical outcomes

Felix Korell; Trisha R Berger; Marcela V Maus

doi:10.1016/j.medj.2022.05.001

Understanding CAR T cell-tumor interactions: Paving the way for successful clinical outcomes

Med. 2022 Aug 12;3(8):538-564. doi: 10.1016/j.medj.2022.05.001.

Authors

Felix Korell¹, Trisha R Berger², Marcela V Maus³

Affiliations

¹ Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA.
² Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
³ Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mvmaus@mgh.harvard.edu.

PMID: 35963235
DOI: 10.1016/j.medj.2022.05.001

Abstract

Since their approval 5 years ago, chimeric antigen receptor (CAR) T cells have gained great importance in the daily clinical practice and treatment of hematological malignancies, although many challenges to their use remain, such as limited long-term CAR T cell efficacy due to disease resistance or recurrence. After a brief overview of CAR T cells, their approval, therapeutic successes, and ongoing limitations, this review discusses what is known about CAR T cell activation, their expansion and persistence, their mechanisms of cytotoxicity, and how the CAR design and/or tumor-intrinsic factors influence these functions. This review also examines the role of cytokines in CAR T cell-associated toxicity and their effects on CAR T cell function. Furthermore, we discuss several resistance mechanisms, including obstacles associated with CAR treatment of solid tumors. Finally, we provide a future outlook on next-generation strategies to further optimize CARs and improve clinical outcomes.

Keywords: CAR T cells; efficacy; immunologic synapse; intrinsic tumor resistance; limitations; tumor microenvironment.

Publication types

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

MeSH terms

Humans
Immunotherapy, Adoptive / adverse effects
Neoplasms* / therapy
Receptors, Antigen, T-Cell / genetics
Receptors, Chimeric Antigen*
T-Lymphocytes

Substances

Receptors, Antigen, T-Cell
Receptors, Chimeric Antigen