Abstract 1524: Effect of a chimeric antibody targeting CXCL1 in bladder cancer

Abstract Introduction and Objectives: Chemokine (C-X-C motif) ligand 1 (CXCL1) plays a crucial role in tumor initiation, promotion, and progression in bladder cancer (BCa) development. Previously, we reported on a monoclonal murine antibody (HL2401) towards CXCL1 which was capable of inhibiting growth in both in vitro and in vivo models. Herein, we have developed a chimeric anti-CXCL1 antibody, which is partially human (cHL2401). In this study, we tested the effect of cHL2401 on tumor growth and angiogenesis in both in vitro and in vivo models. Methods: We developed chimeric anti-human CXCL1 antibody (cHL2401), and then tested for the following: ability to inhibit in vitro angiogenesis, ability to inhibit cellular proliferation, and tumor growth in cell line-derived xenograft model. Results: We first performed the tube formation assay to evaluate the effect on angiogenesis. cHL2401 significantly inhibited tube formation in HUVEC, suggesting that cHL2401 inhibits angiogenesis. The inhibitory effect was better than bevacizumab (FDA-approved drug, anti-VEGF antibody). Next, we performed the cell proliferation assay to evaluate the effect on tumor growth in vitro. cHL2401 significantly inhibited the cell proliferation of T24 and 253J cell lines highly expressing CXCL1. Finally, we tested the effect of cHL2401 on tumor growth in an animal model. Both 8 and 32 mg/kg (i.p., twice weekly) significantly inhibited the tumor growth. The final volume of control tumor was 224.5 mm3, while those of 8 and 32 mg/kg were 102.9 and 93.08, respectively. Conclusions: The chimeric antibody, cHL2401 contains human constant domains and mouse variable domains of mouse HL2401 antibody. Species-matched chimeric antibodies reduce anti-species immune responses in animal models. In this study, we tested whether the effects of mouse HL2401 that we have reported were induced by neutralizing CXCL1 by antibody. Taken together, the results suggest that neutralizing CXCL1 by antibody could be a promising therapeutic agent in BCa. Citation Format: Nari Kim, Hideki Furuya, Kaoru Murakami, Charles J. Rosser. Effect of a chimeric antibody targeting CXCL1 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1524.