| Autor: |
Charles David James, Irina V. Balyasnikova, Christina Amidei, Craig Horbinski, Markella Zanikou, Maciej S. Lesniak, Katarzyna C. Pituch, Nicola Bertolino, Madina Sukhanova, Michael Chastkofsky, Liliana Ilut, Karen S. Aboody, Daniele Procissi, Ting Xiao |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.07.21.188441 |
| Popis: |
Glioblastoma (GBM) is the most lethal primary brain tumor in adults. There is no treatment that provides durable relief for the vast majority of GBM patients. In this study, we’ve tested a bispecific antibody comprised of single-chain variable regions (scFvs) against T cell CD3ε and GBM cell interleukin 13 receptor alpha 2 (IL13Rα2). We demonstrate that this BiTE (BiTELLON) engages peripheral and tumor-infiltrating lymphocytes harvested from patient’s tumors, and in so doing exerts anti-GBM activityex vivo. The interaction of BiTELLONwith T cells and engagement of IL13Rα2-expressing GBM cells stimulates T cell proliferation as well as production of pro-inflammatory cytokines INFγ and TNFα. We have modified neural stem cells (NSCs) to produce and secrete the BiTE (NSCsLLON). When injected intracranially in mice with brain tumor, NSCsLLONshow tropism for tumor, secrete BiTELLON, and remain viable for several days. When injected directly into tumor, NSCLLONprovide significant survival benefit to mice bearing IL13Rα2+ GBM. Our results support further investigation and development of this therapeutic for clinical translation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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