A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer

Abstract

Prostate cancer is one of the most common causes of cancer and osteoclast activation in the bone. To investigate the anti-death in men worldwide, and the treatment options are limited for tumor mechanism of ENO1 mAb, we found that blocking patients with advanced stages of prostate cancer. Upon oncogenic surface ENO1 significantly reduced VEGF-A–induced tube for- or inflammatory stimulation, tumor cells or immune cells express mation of endothelial cells in vitro. Furthermore, HuL227 cell surface enolase-1 (ENO1) as plasminogen receptor to facilitate inhibited inflammation-enhanced osteoclasts activity and the their migration via plasmin activation. Little is known about the secretion of invasion-related cytokines CCL2 and TGFb from roles of ENO1 in prostate cancer, especially in the tumor micro-osteoclasts. In addition, inflammation-induced migration and environment (TME). We hypothesized that targeting surface chemotaxis of androgen-independent prostate cancer cells were ENO1 with specific mAbs would exert multifactorial therapeutic dose-dependently inhibited by HuL227. In summary, we showed potentials against prostate cancer. In vivo, we showed ENO1 mAb that, ENO1 mAb targets multiple TME niches involved in (HuL227) reduced the growth of subcutaneous PC-3 xenograft, prostate cancer progression and bone metastasis via a plasmin-monocytes recruitment, and intratumoral angiogenesis. In a PC-3 related mechanism, which may provide a novel immunotherapy intratibial implantation model, HuL227 reduced tumor growth approach for men with advanced prostate cancer.