Abstract: PO0249
The Effect of ANG-3777 on the Growth of c-MET-Expressing Human Tumor Cells in Immunocompromised Mice
Session Information
- AKI Mechanisms - 3
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Goldberg, Itzhak D., Angion Biomedica Corp, Uniondale, New York, United States
Background
In the injured organs, hepatocyte growth factor (HGF) stimulates c-MET, leading to the activation of intracellular pathways involved in tissue repair. ANG-3777 is an HGF mimetic. In a Phase 2 study, renal transplantation patients with signs of delayed graft function treated with ANG-3777 showed renal function improvement relative to placebo up to 1 year post-transplantation. However, uncontrolled activation of c-MET can stimulate tumor growth. The objective of these studies was to assess the potential of ANG-3777 to stimulate tumor growth in human cell lines.
Methods
c-MET-expressing human tumor xenografts (U87-MG glioma cells, HT29 colon cancer cells, and SUIT-2 pancreatic ductal carcinoma cells) were implanted into 20 BALB/c nude mice per xenograft model. The animals were administered an intraperitoneal injection of 2 mg/kg ANG-3777 or vehicle (dimethyl sulfoxide) daily for up to 28 days. Overall survival (glioma transplant model) and tumor growth and weight (colon and pancreatic tumor xenograft models) were assessed.
Results
Overall survival did not differ in animals treated with ANG-3777 vs vehicle. No significant increase in tumor growth or weight was observed with ANG-3777 treatment. ANG-3777 significantly reduced the mean volume of pancreatic tumors (1747 vs 923.3 mm3, p<0.01;), but not the weight of the tumor (Fig. 1 A&B).
Conclusion
Administration of ANG-3777 in human tumor cells expressing c-MET was not associated with increased tumor volume or weight in pancreatic and colon tumor models and did not increase mortality in the glioma model in BALB/c nude mice.