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Related Experiment Video

Updated: Feb 13, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

Chimeric Antigen Receptor T Cell-Mediated Neurotoxicity in Nonhuman Primates.

Agne Taraseviciute^1,2,3, Victor Tkachev^1,2,3, Rafael Ponce⁴

¹The Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington.

Cancer Discovery

|March 23, 2018

Summary

This summary is machine-generated.

Researchers developed a new nonhuman primate model to study neurotoxicity from CAR T-cell therapy. This model shows T-cells and cytokines cause brain inflammation, aiding the development of safer immunotherapies.

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Area of Science:

Immunotherapy
Oncology
Neuroscience

Background:

Chimeric antigen receptor (CAR) T-cell immunotherapy is effective against leukemias and lymphomas but causes toxicities like cytokine release syndrome (CRS) and neurotoxicity.
A lack of relevant models hinders the development of therapies to prevent CAR T-cell-mediated neurotoxicity.

Purpose of the Study:

To establish a clinically relevant nonhuman primate (NHP) model for studying CAR T-cell-induced neurotoxicity.
To investigate the immunological mechanisms underlying CAR T-cell-mediated neurotoxicity.

Main Methods:

Adoptive transfer of autologous CD20-specific CAR T cells into rhesus macaques (RMs) following cyclophosphamide lymphodepletion.
Monitoring of CAR T-cell expansion, clinical toxicities (CRS and neurotoxicity), serum and cerebrospinal fluid (CSF) cytokine levels.
Analysis of T-cell infiltration in CSF and brain parenchyma during neurotoxicity.

Main Results:

CD20 CAR T cells expanded robustly in RMs, inducing CRS and neurotoxicity.
Neurotoxicity was associated with elevated serum and CSF inflammatory cytokines, including IL6, IL2, GM-CSF, and VEGF.
Both CAR T cells and non-CAR T cells infiltrated the CSF and brain parenchyma during neurotoxicity, leading to pan-T cell encephalitis.

Conclusions:

The developed RM model is the first immunologically relevant NHP model for studying CRS and neurotoxicity associated with B cell-directed CAR T-cell therapy.
CAR T-cell-mediated neurotoxicity involves proinflammatory CSF cytokines and a pan-T cell encephalitis characterized by T-cell infiltration in the brain.