Neurological implications of chimeric antigen receptor-T cell therapy

Area of Science:

• Immunology
• Neuroscience
• Oncology

Background:

• Chimeric antigen receptor (CAR)-T cell therapy is effective for hematological cancers and is being explored for autoimmune diseases.
• CAR-T therapy induces deep B-cell depletion, potentially leading to long-term remission.
• Neurological toxicities, including ICANS and peripheral nerve syndromes, limit broader application.

Purpose of the Study:

• To review the biological principles of CAR-T cell therapy.
• To summarize emerging data on CAR-T cell use in neuroimmunology.
• To describe the spectrum, timing, and mechanisms of CAR-T cell-related neurotoxicity.

Main Methods:

• Review of data from oncology and early autoimmune trials.
• Analysis of clinical presentation, timing, and proposed mechanisms of neurotoxicity.
• Distinguishing immune effector cell-associated neurotoxicity syndrome (ICANS) from later toxicities.

Main Results:

• CAR-T therapy shows promise for autoimmune diseases but presents significant neurological risks.
• Neurotoxicities range from ICANS to movement, cerebellar, cranial nerve, and peripheral nerve syndromes.
• Understanding the distinct profiles of early versus later neurotoxicities is key.

Conclusions:

• Neurologists require comprehensive knowledge of CAR-T cell therapy's benefits and risks for neuroimmunological applications.
• Multidisciplinary collaboration is essential for the safe administration of CAR-T cell therapies.
• Further research is needed to manage and mitigate CAR-T cell-related neurotoxicity.