Potent anti-angiogenesis and anti-tumor activity of a novel human anti-VEGF antibody, MIL60

Abstract

Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor (VEGF) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin (the KD value of MIL60 was 44.5pM, while that of Avastin was 42.7pM). MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation (the IC50 value of MIL60 was 31±6.4ng/ml and that of Avastin was 47±8.1ng/ml), migration (8µg/ml or 0.8µg/ml MIL60 versus the control: P<0.05) and tube formation (2µg/ml or 0.2µg/ml MIL60 versus the control: P<0.05) via the VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis (MIL60 versus N.S.: P=0.0007; Avastin versus N.S.: P=0.00046). These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.