In Vitro Evaluation of Genetically Unmodified Ligand-Armed Allogeneic Natural Killer Cells to Treat EGFR-Positive Glioblastoma.

in Cells by Hortense Courot, Emilie Rigal, Nawfel Adib, Marc Criton, Alan Cookson, Bénédicte Fauvel, Jessy Presumey

TLDR

  • Researchers have developed Pin-EGFR-armed eNK cells as a potential therapy against glioblastomas with EGFR gene amplification or mutation.
  • Pin-EGFR-armed eNK cells demonstrate specific, rapid, and potent cytotoxicity against GBM cell lines and patient-derived cells in vitro.
  • This engineered cell therapy shows promise for targeting residual tumor tissue following GBM surgery and improving patient care.

Abstract

Glioblastomas (GBMs) are lethal brain tumors in which EGFR gene amplification or mutation is frequently detected and is associated with poor prognosis. The standard of care is maximal resection followed by chemotherapy and radiation. Over the last twenty years, marginal improvements in patient survival have been achieved mainly through surgical techniques and the more accurate use of radiation. In this study, umbilical cord blood-derived and expanded human allogeneic natural killer (eNK) cells were pre-complexed to an Fc-engineered anti-EGFR monoclonal antibody (Pin-EGFR) to create Pin-EGFR-armed eNK cells. Pin-EGFR-armed eNK cells showed in vitro persistence of mAb anchoring. This arming process mediated specific, rapid and potent NK cell-redirected cytotoxicity against GBM cell lines and patient-derived cells in models consistent with the pathophysiological conditions of GBM. These results demonstrate the potential of Pin-EGFR-armed eNK cells to be an effective therapy against GBM cell lines in vitro. This product represents a promising strategy to directly target residual tumor tissue remaining at and beyond the resection margins immediately following GBM surgery to improve patient care.

Overview

  • The study examines the use of Pin-EGFR-armed eNK cells as a potential therapy against glioblastomas (GBMs) that have EGFR gene amplification or mutation.
  • The researchers used human allogeneic natural killer (eNK) cells derived from umbilical cord blood, which were pre-complexed to an Fc-engineered anti-EGFR monoclonal antibody (Pin-EGFR) to create Pin-EGFR-armed eNK cells.
  • The primary objective is to demonstrate the effectiveness of Pin-EGFR-armed eNK cells against GBM cell lines and patient-derived cells in vitro.

Comparative Analysis & Findings

  • Pin-EGFR-armed eNK cells showed persistence of mAb anchoring in vitro, indicating a specific and potent cytotoxicity against GBM cell lines and patient-derived cells.
  • The study demonstrates that Pin-EGFR-armed eNK cells can redirect cytotoxicity against GBM cells, showing rapid and potent killing of GBM cell lines and patient-derived cells in vitro.
  • The results suggest that Pin-EGFR-armed eNK cells can be an effective therapy against GBM cell lines in vitro.

Implications and Future Directions

  • The study's findings imply that Pin-EGFR-armed eNK cells could be an effective strategy to target residual tumor tissue remaining at and beyond the resection margins immediately following GBM surgery.
  • Future studies should investigate the safety and efficacy of Pin-EGFR-armed eNK cells in clinical trials to assess their potential as a treatment for glioblastomas.
  • Further research is needed to explore the optimal dosing and schedule of Pin-EGFR-armed eNK cells, as well as the combination of this therapy with standard of care treatments.
Read Full Article