Development of a broadly potent neutralizing antibody targeting Nidogen 1 effectively inhibits cancer growth and metastasis in preclinical tumor models

Abstract

Background and Objectives: Nidogen 1 (NID1) is a highly conserved structural component of the extracellular matrix (ECM), which interacts with different basement membrane (BM) proteins to form a stabilized meshwork. The promoting ability of NID1 in cancer development and metastasis has been demonstrated in multiple cancer types, including ovarian cancer, breast cancer, and hepatocellular carcinoma (HCC). This suggests that NID1 holds great potential as a therapeutic target for cancer treatment. However, currently, there is a lack of commercially available neutralizing antibody for clinical testing and treatment. Methods: To address this, we utilized hybridoma technology to develop a monoclonal neutralizing antibody which targets the critical G2 region of NID1. The therapeutic effect of this NID1 neutralizing antibody against a wide range of human cancer cells was evaluated. Results: The results showed that NID1 neutralizing antibody effectively attenuated the growth, motility and metastasis of HCC, lung cancer, breast cancer and nasopharyngeal carcinoma cells in vitro. The proof-of-concept of targeting NID1 using neutralizing antibody was further demonstrated in various animal models. Mechanistically, our findings indicate that treatment with NID1 neutralizing antibody leads to the deregulation of hypoxia-inducible factor-1 (HIF-1α) pathway in cancer cells. Conclusions: Taken together, this study offers promising prospects for a new pan-cancer monoclonal antibody-based strategy by targeting the tumor-associated membrane protein NID1.