Related Experiment Video
Updated: Jun 14, 2025
Intracranial Cannula Implantation for Serial Locoregional Chimeric Antigen Receptor CAR T Cell Infusions in Mice
Published on: February 24, 2023
CAR-T Cells in the Treatment of Nervous System Tumors
Ugo Testa1, Germana Castelli1, Elvira Pelosi1
1Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Abstract:
Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy has been particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity, the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising antitumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies.
Insights
Chimeric antigen receptor T cell (CAR-T) therapy shows promise for brain tumors but faces challenges like tumor heterogeneity and immunosuppression. Advanced CAR-T designs and combination therapies are needed to improve efficacy against these solid tumors.
Area of Science:
- Immunology
- Oncology
- Neuroscience
Background:
- Chimeric antigen receptor T cells (CAR-Ts) are effective against blood cancers but show limited success in solid tumors.
- Brain tumors are a key focus for CAR-T cell therapy research due to the potential for improved treatments.
Purpose of the Study:
- To review the challenges and recent advancements in CAR-T cell therapy for brain tumors.
- To identify strategies for enhancing CAR-T cell efficacy in the brain tumor microenvironment.
Main Methods:
- Review of recent scientific literature on CAR-T cell therapy in brain tumors.
- Analysis of factors limiting CAR-T cell activity in solid tumors, specifically brain cancers.
- Evaluation of emerging CAR-T cell designs and combination therapy approaches.
Main Results:
- CAR-T cell therapy faces significant hurdles in brain tumors, including antigen heterogeneity, poor T cell infiltration and persistence, and a suppressive tumor microenvironment.
- Despite challenges, some CAR-T cell therapies (GD2-CAR-T, CARv3-TEAM-E) show early promise in specific brain tumors like diffuse midline gliomas, neuroblastomas, and glioblastomas.
Conclusions:
- Overcoming the immunosuppressive brain tumor microenvironment and improving CAR-T cell targeting are crucial for therapeutic success.
- Future strategies should focus on advanced CAR-T cell engineering, such as multi-antigen targeting, and integrating combination therapies to enhance antitumor responses.
