Systemic anti-HGF monoclonal antibody therapy induces regression of intracranial glioma xenograft

Abstract

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Hepatocyte growth factor (HGF) and its receptor Met are involved in the initiation, progression and metastasis of numerous systemic and CNS tumors. Thus, an anti-HGF monoclonal antibody (mAb) capable of blocking the HGF-Met interaction could have broad applicability in cancer therapy. An anti-HGF mAb L2G7 that blocks binding of HGF to Met was generated by hybridoma technology, and its ability to inhibit various biological activities of HGF was measured by in vitro assays. MAb L2G7 strongly inhibited biological activities of HGF measured in vitro, including cell proliferation, and cell scattering. The ability of L2G7 to inhibit growth of tumors was determined by establishing subcutaneous and intracranial xenografts of human U87 and U118 glioma cell lines in nude mice, and treating with 50-100 μg L2G7 or control administered intraperitoneally twice per week. Treatment with L2G7 completely inhibited growth of established subcutaneous xenografts in nude mice. Moreover, systemic administration of L2G7 from Day 5 induced regression of intracranial U87 xenografts and dramatically prolonged survival of tumor-bearing mice from a median of 39 days to over 90 days. L2G7 treatment of large intracranial tumors (average tumor size, 26.7 mm³) from Day 18 induced substantial tumor regression (control group, 134.3 mm³; L2G7 treated group, 11.7 mm³) by Day 29 and again prolonged animal survival.