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

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 feas...

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Bibliographic Details
Published in:	Nature communications Vol. 12; no. 1; p. 3615
Main Authors:	Rousso-Noori, Liat, Mastandrea, Ignacio, Talmor, Shauli, Waks, Tova, Globerson Levin, Anat, Haugas, Maarja, Teesalu, Tambet, Alvarez-Vallina, Luis, Eshhar, Zelig, Friedmann-Morvinski, Dinorah
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 14-06-2021 Nature Publishing Group Nature Portfolio
Subjects:	13 13/106 13/31 13/51 14/19 42 42/44 59 59/5 631/67/1059/2325 631/67/1922 64/60 692/4028/67/1922 Animal models Antiangiogenics Antigens Cell culture Cell therapy Chimeric antigen receptors Endothelial cells Feasibility studies Glioblastoma Glioma Glioma cells Heterogeneity Humanities and Social Sciences Lymphocytes Lymphocytes T multidisciplinary Patients Receptors Science Science (multidisciplinary) Tumors Xenografts Xenotransplantation
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Summary:	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. Chimeric antigen receptor (CAR) T cell therapy has been proposed as a promising approach for treating glioblastoma. Here the authors show that p32 is expressed in murine and human glioma and that p32-directed CAR-T cells promote anti-tumor responses in preclinical models by targeting glioma cells and tumor derived endothelial cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-23817-2