Get started
Work

Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma

Year: 2026
Type: article
Abstract: Chimeric antigen receptor (CAR) T-cell therapy has shown early promise against glioblastoma, which lacks effective treatment options. However, two key challenges curtail efficacy: tumor-antigen heterogeneity and an immunosuppressive tumor microenvironment. CAR T cells engineered to secrete combinations of immunomodulatory proteins can reverse immune suppression and engage endogenous immunity. Through head-to-head in vivo comparisons of potentially synergistic armor combinations, we demonstrated that T cells expressing a CAR plus IL12 and the decoy-resistant form of IL18 (CAR-12.DR18 T cells) show strong efficacy against antigen-heterogeneous glioma in immunocompetent mice. Robust antitumor efficacy with effective toxicity mitigation was achieved via combined administration of CAR-12.DR18 T cells with CAR T cells that secrete an anti-vascular endothelial growth factor (anti-VEGF) single-chain variable fragment (scFv). This combination therapy presents a clinically applicable strategy to overcome key barriers to the effective treatment of glioblastoma. SIGNIFICANCE: CAR-T cells armored with cytokines and anti-VEGF single-chain variable fragments can control orthotopic, antigen-heterogeneous glioma with minimal toxicity, providing a therapeutic strategy for glioblastoma patients in urgent need of efficacious treatments.
DOI: 10.1158/0008-5472.can-26-1515
Authors: Justin D. Clubb, Ryan M. Shih, Torahito A. Gao, Amanda Shafer, Shreya Vajragiri, Katrina Lam, Sohan Talluri, Amber Bouren, Christine E. Brown, Pedro Ruivo, Robert M. Prins, Han-Chung Wu, Yvonne Y. Chen
Institutions: University of California, Los Angeles, City Of Hope National Medical Center, Beckman Research Institute, University of California, Davis, UCLA Jonsson Comprehensive Cancer Center, Institute of Cellular and Organismic Biology, Academia Sinica, Academia Sinica
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: green
Funders: Cancer Research Institute, National Institutes of Health, University of California, Los Angeles, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Science Foundation Graduate Research Fellowship Program
Awards: G5035639098, UCLA-Caltech Medical Scientist Training Program, Programming multi-pronged immune response to glioblastoma with IL-13Ra2/TGF-b CAR-T cell therapy., G7130865185, Neoadjuvant checkpoint blockade for recurrent glioblastoma, UCLA SPORE in Brain Cancer, UCLA Tumor Immunology Institutional Training Grant, UCLA-Caltech Medical Scientist Training Program
OpenAlex ID: W7161829133
FWCI: 10.37
Cites:
Cited by: 4
Related to: 10