[Abstract] 

Previous report has shown that P5, an antibody to integrin beta 1 (ITGB1), has an anti-cancer effects on A549, a non-small cell lung cancer (NSCLC) cell line. Since overexpression of ITGB1 has been reported to be a cause of resistance to various anti-cancer therapy, such as cytotoxic chemotherapy, there is a need for an effective therapeutic antibody to inhibit ITGB1. Here, we describe a novel humanized anti-ITGB1 antibody, GP5 and its anti-cancer effects. GP5 was generated by grafting 6 CDRs from P5, the previously generated mouse antibody, onto a human antibody framework. The binding affinity of GP5 to ITGB1 was similar to that of P5. GP5 showed a specific binding only to ITGB1 regardless of alpha subunits. In in vitro assay, GP5 showed increased apoptosis in A549 than P5 and GP5 could induce the internalization of ITGB1 after binding with it, thereby reducing the concentration of ITGB1 on the surface of A549. In addition, GP5 could increase sensitivity of gefitinib in PC9GR, a gefitinib resistance NSCLC cell. Furthermore, GP5 itself could reduce tumor size in tumor xenograft mouse, and its effect was significantly increased in combination with cisplatin. Specifically, tumor size did not increase even after the discontinuation of treatment in group of combining GP5 with cisplatin. In conclusion, the novel humanized antibody, GP5 is expected to be a effective therapeutic agent for NSCLC either as single-agent therapy or combination with cytotoxic chemotherapies.