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Nat Commun ; 12(1): 3615, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127674

RESUMO

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.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Glioma/imunologia , Glioma/terapia , Linfócitos T/imunologia , Idoso , Animais , Antígenos de Neoplasias/imunologia , Neoplasias Encefálicas , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/metabolismo , Humanos , Imunoterapia Adotiva , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Proteínas Mitocondriais/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Serina Endopeptidases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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