Antitumor activity of a ROR1 × CD3 bispecific antibody in non-small cell lung cancer

Abstract

Over the last decade, immuno-oncologic drugs especially CD3-engaging bispecific antibodies (biAbs) are experiencing fast-paced evolution, but big challenges still exist in the clinical development of biAbs in solid tumors, especially non-small cell lung cancer (NSCLC). In this study, we choose a ROR1 × CD3 biAb in scFv-Fc format, named R11 × v9 biAb, to investigate its tumor-inhibiting role in NSCLC. Notably, the ROR1-engaging arm binds both human and mouse ROR1. We found that R11 × v9 biAb specifically binds T cells and tumor cells simultaneously, and dose-dependent cytotoxicity was detected for various ROR1⁺ NSCLC cell lines. Further, R11 × v9 biAb mediated T-cell derived proinflammatory cytokine secretion, boosted granzyme B and perforin production from CD8⁺ T cells, and recruited more CD4⁺ T cells and CD8⁺ T cells into the tumor tissues. The antitumor activity of R11 × v9 biAb was confirmed in two xenograft mouse models of ROR1⁺ NSCLC. Importantly, no harmful side effects were observed in these in vivo studies, warranting further preclinical and clinical studies of R11 × v9 biAb in NSCLC.

Keywords: Bispecific antibodies; NSCLC; ROR1; T cells; Tumor immunotherapy.