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, Dinorah Friedmann-Morvinski

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3615
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021

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