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

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.