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

Over the last decade, immuno-oncologic drugs especially CD3-engaging bispecific antibodies (biAbs) are expe-riencing 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 x CD3 biAb in scFv-Fc format, named R11 x 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 x v9 biAb specifically binds T cells and tumor cells simul-taneously, and dose-dependent cytotoxicity was detected for various ROR1+ NSCLC cell lines. Further, R11 x 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 x 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 x v9 biAb in NSCLC.

Automated summary

Over the last decade, immuno-oncologic drugs, particularly CD3-engaging bispecific antibodies (biAbs), have seen rapid development. However, there are still significant challenges in their clinical development for solid tumors, especially non-small cell lung cancer (NSCLC). In this study, a ROR1 x CD3 biAb, called R11 x v9 biAb, was investigated for its tumor-inhibiting role in NSCLC. The biAb demonstrated specific binding to T cells and tumor cells, dose-dependent cytotoxicity against various ROR1+ NSCLC cell lines, and promoted immune responses in tumor tissues. The antitumor activity of R11 x v9 biAb was confirmed in mouse models of ROR1+ NSCLC without observed side effects, supporting further preclinical and clinical studies.