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

Katarzyna C. Pituch, Markella Zannikou, Liliana Ilut, Ting Xiao, Michael Chastkofsky, Madina Sukhanova, Nicola Bertolino, Daniele Procissi, Christina Amidei, Craig M. Horbinski, Karen S. Aboody, C. David James, Maciej S. Lesniak, Irina V. Balyasnikova*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 CD3e 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.

Original languageEnglish (US)
Article numbere2015800118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number9
DOIs
StatePublished - Mar 2 2021

Keywords

  • Bispecific T cell engagers
  • Delivery
  • GBM
  • Immunotherapy
  • Neural stem cells

ASJC Scopus subject areas

  • General

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