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CAR T-cells to treat brain tumors
Grace Guzman1, Karolina Pellot2, Megan R Reed3
1Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Abstract:
Tremendous success using CAR T therapy in hematological malignancies has garnered significant interest in developing such treatments for solid tumors, including brain tumors. This success, however, has yet to be mirrored in solid organ neoplasms. CAR T function has shown limited efficacy against brain tumors due to several factors including the immunosuppressive tumor microenvironment, blood-brain barrier, and tumor-antigen heterogeneity. Despite these considerations, CAR T-cell therapy has the potential to be implemented as a treatment modality for brain tumors. Here, we review adult and pediatric brain tumors, including glioblastoma, diffuse midline gliomas, and medulloblastomas that continue to portend a grim prognosis. We describe insights gained from different preclinical models using CAR T therapy against various brain tumors and results gathered from ongoing clinical trials. Furthermore, we outline the challenges limiting CAR T therapy success against brain tumors and summarize advancements made to overcome these obstacles.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for brain tumors, but faces challenges like the tumor microenvironment. Research is exploring preclinical models and clinical trials to overcome these obstacles for better CAR T efficacy.
Area of Science:
- Oncology
- Immunotherapy
- Neuro-oncology
Background:
- CAR T-cell therapy has achieved significant success in treating hematological malignancies.
- Translating CAR T-cell therapy to solid tumors, particularly brain tumors, remains a challenge.
- Existing barriers include the immunosuppressive tumor microenvironment, blood-brain barrier, and tumor-antigen heterogeneity.
Purpose of the Study:
- To review the current state of CAR T-cell therapy for adult and pediatric brain tumors.
- To explore insights from preclinical models and ongoing clinical trials.
- To identify challenges and advancements in overcoming obstacles for CAR T-cell therapy in brain tumors.
Main Methods:
- Review of preclinical studies using CAR T-cell therapy against various brain tumors.
- Analysis of data from ongoing clinical trials involving CAR T-cell therapy for brain tumors.
- Identification and summary of challenges and proposed solutions for CAR T-cell therapy efficacy.
Main Results:
- CAR T-cell therapy has demonstrated limited efficacy in solid tumors compared to blood cancers.
- Preclinical models and early clinical trials provide insights into CAR T-cell behavior in the brain tumor microenvironment.
- Specific brain tumors like glioblastoma, diffuse midline gliomas, and medulloblastomas are areas of focus.
Conclusions:
- Despite significant challenges, CAR T-cell therapy holds potential as a treatment for brain tumors.
- Overcoming the immunosuppressive tumor microenvironment and blood-brain barrier are critical for success.
- Continued research in preclinical models and clinical trials is essential to advance CAR T-cell therapy for brain cancers.
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