The immunologic aspects of cytokine release syndrome and graft versus host disease following CAR T cell therapy

Abstract

Chimeric antigen receptor (CAR) T cells are the pioneers of cancer immunotherapy, which to this date have several FDA-approved products. They have been substantially improved since their first introduction in 1993 and have shown promising results regardless of their inevitable side effects. Cytokine release syndrome (CRS), the most common toxicity after CAR T cell treatment, is affiliated to a systemic inflammation through surge of cytokines, mainly IL-6, IL-1, and INF-γ. Furthermore, difference between histocompatibility antigens activates the graft versus host disease (GvHD) effect of the allogenic CAR T cells against the host cells. Immunological reactions induced by CAR T cells in the form of CRS or GvHD is necessary for fostering good responses, while excess reactions can potentially threaten patient life. In this review, we first describe the history, applications, and structure of CAR T cells, followed by a comprehensive review of CRS regarding its definition, management, and immunological aspects. Finally, we discuss about the clinical aspects of CRS and GvHD after CAR T cell therapy and how to harness anti-tumoral effects, while mitigating the adverse effects.

Graphical Abstract

Declaration of interest

No potential conflict of interest was reported by the authors.

Authors contribution

VM conceptualized the title and prepared the first draft. NY edited and revised the manuscript and finalized the draft. NR critically revised the manuscript, finalized the draft, and supervised the project. All the authors have read and approved the final draft of the manuscript.

Funding

The author(s) reported there is no funding associated with the work featured in this article.