Neural stem cells secreting bispecific T cell engager to induce selective antiglioma activity.
Proc Natl Acad Sci U S A
; 118(9)2021 03 02.
Article
em En
| MEDLINE
| ID: mdl-33627401
ABSTRACT
Glioblastoma (GBM) is the most lethal primary brain tumor in adults. No treatment provides durable relief for the vast majority of GBM patients. In this study, we've tested a bispecific antibody comprised of single-chain variable fragments (scFvs) against T cell CD3ε and GBM cell interleukin 13 receptor alpha 2 (IL13Rα2). We demonstrate that this bispecific T cell engager (BiTE) (BiTELLON) engages peripheral and tumor-infiltrating lymphocytes harvested from patients' tumors and, in so doing, exerts anti-GBM activity ex vivo. The interaction of BiTELLON with T cells and IL13Rα2-expressing GBM cells stimulates T cell proliferation and the production of proinflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα). We have modified neural stem cells (NSCs) to produce and secrete the BiTELLON (NSCLLON). When injected intracranially in mice with a brain tumor, NSCLLON show tropism for tumor, secrete BiTELLON, and remain viable for over 7 d. When injected directly into the tumor, NSCLLON provide a significant survival benefit to mice bearing various IL13Rα2+ GBMs. Our results support further investigation and development of this therapeutic for clinical translation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T
/
Glioblastoma
/
Imunomodulação
/
Células-Tronco Neurais
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article