P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas
| Autor: | Shauli Talmor, Ignacio Mastandrea, Tova Waks, Zelig Eshhar, Liat Rousso-Noori, Dinorah Friedmann-Morvinski, Tambet Teesalu, Maarja Haugas, Luis Álvarez-Vallina, Anat Levin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment T-Lymphocytes General Physics and Astronomy Angiogenesis Inhibitors Cancer immunotherapy Immunotherapy Adoptive Mice 0302 clinical medicine Receptor Multidisciplinary Receptors Chimeric Antigen Brain Neoplasms Serine Endopeptidases Glioma Tumor-Derived medicine.anatomical_structure 030220 oncology & carcinogenesis Female T cell Science Receptors Antigen T-Cell Mice Nude Antineoplastic Agents General Biochemistry Genetics and Molecular Biology Article Mitochondrial Proteins 03 medical and health sciences Antigen Antigens Neoplasm Cell Line Tumor medicine Animals Humans neoplasms Aged business.industry General Chemistry Immunotherapy medicine.disease Xenograft Model Antitumor Assays Chimeric antigen receptor nervous system diseases Mice Inbred C57BL CNS cancer body regions 030104 developmental biology Cell culture Cancer research business Carrier Proteins Glioblastoma |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Rousso-Noori, L, Mastandrea, I, Talmor, S, Waks, T, Globerson Levin, A, Haugas, M, Teesalu, T, Alvarez-Vallina, L, Eshhar, Z & Friedmann-Morvinski, D 2021, ' P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas ', Nature Communications, vol. 12, no. 1, 3615 . https://doi.org/10.1038/s41467-021-23817-2 Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-23817-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink