Neural stem cells secreting bispecific T cell engager to induce selective antiglioma activity.

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) (BiTE^LLON) engages peripheral and tumor-infiltrating lymphocytes harvested from patients' tumors and, in so doing, exerts anti-GBM activity ex vivo. The interaction of BiTE^LLON 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 BiTE^LLON (NSC^LLON). When injected intracranially in mice with a brain tumor, NSC^LLON show tropism for tumor, secrete BiTE^LLON, and remain viable for over 7 d. When injected directly into the tumor, NSC^LLON provide a significant survival benefit to mice bearing various IL13Rα2⁺ GBMs. Our results support further investigation and development of this therapeutic for clinical translation.

SUBMITTER: Pituch KC 

PROVIDER: S-EPMC7936285 | biostudies-literature |

REPOSITORIES: biostudies-literature