P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas

Liat Rousso-Noori, Ignacio Mastandrea, Shauli Talmor, Tova Waks, Anat Globerson Levin, Maarja Haugas, Tambet Teesalu, Luis Alvarez-Vallina, Zelig Eshhar and Dinorah Friedmann-Morvinski ()
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Liat Rousso-Noori: Tel Aviv University
Ignacio Mastandrea: Tel Aviv University
Shauli Talmor: Tel Aviv University
Tova Waks: Tel Aviv Sourasky Medical Center (TASMC)
Anat Globerson Levin: Tel Aviv Sourasky Medical Center (TASMC)
Maarja Haugas: University of Tartu
Tambet Teesalu: University of Tartu
Luis Alvarez-Vallina: Hospital Universitario 12 de Octubre
Zelig Eshhar: Tel Aviv Sourasky Medical Center (TASMC)
Dinorah Friedmann-Morvinski: Tel Aviv University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Glioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades of research no curative treatment is available and it thus remains associated with a very dismal prognosis. Although recent pre-clinical and clinical studies have demonstrated the feasibility of chimeric antigen receptors (CAR) T cell immunotherapeutic approach in glioblastoma, tumor heterogeneity and antigen loss remain among one of the most important challenges to be addressed. In this study, we identify p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor associated antigen for redirected CAR T cell therapy. We generate p32 CAR T cells and find them to recognize and specifically eliminate p32 expressing glioma cells and tumor derived endothelial cells in vitro and to control tumor growth in orthotopic syngeneic and xenograft mouse models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients.

Date: 2021
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DOI: 10.1038/s41467-021-23817-2

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