Neurological adverse effects of chimeric antigen receptor T-cell therapy

ABSTRACT

Introduction

Chimeric antigen receptor (CAR) T-cell is among the most prevalent approaches that act by directing T-cells toward cancer; however, they need to be optimized to minimize side effects and maximize efficacy before being used as standard treatment for malignancies. Neurotoxicity associated with CAR T-cell therapy has been well-documented in recent works.

Areas covered

In this regard, two established syndromes exist. Immune effector cell-associated neurotoxicity syndrome (ICANS), previously called cytokine release encephalopathy syndrome (CRES), is a neuropsychiatric condition which can occur after therapy by immune effector cells (IEC) and T-lymphocytes utilizing treatments. Another syndrome is cytokine release syndrome (CRS), which may overlap with ICANS.

Expert opinion

ICANS clinical manifestations include cerebral edema, mild lethargy, aphasia, and seizures. Notably, ICANS is associated with changes to EEG and neuroradiological findings. Therefore, it is necessary to make a timely and accurate diagnosis of neurological complications of CAR T-cells by clinical presentations, neuroimaging, and EEG. Since neurological events by different CAR T-cell products are heterogeneous, guides should be developed according to each product. Here, we provide an updated review of general information on CAR T-cell therapies and applications, neurological syndromes associated with their use, and risk factors contributing to ICANS.

KEYWORDS:

• Adoptive T-cell therapy
• adverse events
• CAR T-cell
• drug safety
• Neuroimmunology

Article highlights

• The utility of Chimeric antigen receptor (CAR) T-cells as novel cancer treatments depends on neurotoxicity and other safety parameters.

• Immune effector cell-associated neurotoxicity syndrome (ICANS) is discussed in the context of T-lymphocyte therapies.

• Different CAR T-cell products exhibit varied safety profiles. Manufacturers should exercise caution with each step of T-cell preparation.

• We advise timely and accurate diagnosis of neurological events of CAR T-cells based on clinical presentations, neuroimaging, and EEG.

• Steroid therapy is a major candidate for the therapy of CAR T-cell-associated toxicities. However, the field is in urgent need of next-generation candidates.

• CARs carrying exosomes and inflammasome targeting to regulate cytokines are suggested as robust approaches against T-cell-associated neurotoxicity.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Mohamadi and K Saleki conceptualized the study. M Mohamadi, K Saleki, and P Alijanizadeh prepared the initial draft. K Saleki prepared the final draft. K Saleki and P Alijanizadeh designed the illustration. N Rezaei conceptualized the study, supervised the project, and critically appraised the manuscript. All authors read and approved the final manuscript for publication.

Acknowledgments

We thank the USERN MUBabol Office and Student Research Committee of Babol University of Medical Sciences. Figure created with BioRender.com

Additional information

Funding

This paper was not funded.