CAR-T Cell Therapy: Mechanism, Management, and Mitigation of Inflammatory Toxicities

Joseph W Fischer; Nirjal Bhattarai

doi:10.3389/fimmu.2021.693016

CAR-T Cell Therapy: Mechanism, Management, and Mitigation of Inflammatory Toxicities

Front Immunol. 2021 Jun 18:12:693016. doi: 10.3389/fimmu.2021.693016. eCollection 2021.

Authors

Joseph W Fischer¹, Nirjal Bhattarai¹

Affiliation

¹ Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.

Abstract

Engineered T cell therapies such as chimeric antigen receptor (CAR) expressing T cells (CAR-T cells) have great potential to treat many human diseases; however, inflammatory toxicities associated with these therapies present safety risks and can greatly limit its widespread use. This article briefly reviews our current understanding of mechanisms for inflammatory toxicities during CAR T-cell therapy, current strategies for management and mitigation of these risks and highlights key areas of knowledge gap for future research.

Keywords: CAR-T cells; CRS; inflammation; neurotoxicity; toxicities.

Publication types

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

MeSH terms

Animals
Humans
Immunotherapy, Adoptive / adverse effects*
Inflammation / etiology
Inflammation / immunology
Inflammation / metabolism
Inflammation / prevention & control*
Inflammation Mediators / immunology
Inflammation Mediators / metabolism
Phenotype
Receptors, Chimeric Antigen / genetics
Receptors, Chimeric Antigen / immunology*
Risk Assessment
Risk Factors
Signal Transduction
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
T-Lymphocytes / transplantation*
Treatment Outcome

Substances

Inflammation Mediators
Receptors, Chimeric Antigen