Evaluation of Novel Agents which Target Neovasculature of Breast Tumors
Abstract
The unique fusion toxin VEGF121/rGel can specifically kill both log-phase and confluent vascular endothelial cells expressing the KDR receptor for VEGF(PNAS 99:7866,2002). We have discovered 19 unique genes upregulated(>5 fold) in endothelial cells treated with VEGF121/rGel(confirmed by Western and RT-PCR). VEGF121/rGel(i.v.) treatment had a dramatic cytotoxic effect in both orthotopic and metastatic human breast tumor models. Against the orthotopic model, tumor growth was significantly delayed by 50%. In addition, tumors completely regressed in 3/6 (50%) of treated mice. In the metastatic breast model, treatment with VEGF121/rGel reduced both the number and area of lung foci by 58% and 50% respectively and we demonstrated VEGF121/rGel(by IHC) on lung tumor vasculature but not 2. normal vasculature. In addition, the number of blood vessels per mm in metastatic foci was 198+ 3% versus 388+_21 for treated and control respectively. Approximately 62% of metastatic colonies from the VEGF/rGel treated group had <10 vessels/colony compared to 23% in th1 receptor on blood vessel endothelium was intensely expressed on control tumors, but not expressed on treated tumors. Metastatic foci had a 3 fold lower Ki-67 labeling index compared to control tumors. This suggests that VEGF121/rGel has impressive antitumor activity in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA426085
Entities
People
- Michael Rosenblum
Organizations
- The University of Texas MD Anderson Cancer Center