Angiogenesis is the process by which tumours integrate themselves into the vascular system
Angiogenesis is the process by which tumours grow new blood vessels and integrate themselves into the vascular system. Integrins are believed to be involved in the process; these are dimeric proteins comprising two subunits, termed a and b, and the a5b1 integrin is thought to be proangiogenic. This integrin and its receptor, also known as fibronectin, are upregulated in tumour vasculature, and the receptor is overexpressed in angiogenic endothelial cells. Thus this may be a useful target for oncolytic agents, and Biogen Idec’s experimental monoclonal antibody volociximab works in this way.1
In a Phase I trial, 21 patients with advanced solid tumours were given a total of 223 escalating intravenous infusions of volociximab, at doses from 0.5 to 15mg/kg.2 One with metastatic renal cell carcinoma that was refractory to sunitinib had a minor response, and five with progressive tumours achieved stable disease for at least four months, including one with metastatic melanoma whose stable disease lasted 14 months.
Its potential in combinations is also being investigated, including with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.3 A total of 22 patients were given doses of up to 30mg/kg plus the other two agents every three weeks, of whom six had a partial response and 12 stable disease.
In a Phase II trial 40 patients with metastatic renal cell carcinoma were given 10mg/kg of volociximab every two weeks until disease progression, 21 of whom had previously had antiangiogenic therapy.4 There was one confirmed partial response, and 80% achieved stable disease for at least two and up to 22 months. However, Phase II trials in ovarian, peritoneal and metastatic melanoma were less successful.
1. R. Vanitha et al. Proc. Am. Assoc. Cancer Res 2003, 44(2), Abst 3052
2. A.D. Ricart et al. Clin. Cancer Res. 2008, 24, 7924
3. B. Besse et al. J. Clin. Oncol. 2009, 27 (15, Suppl.) Abst e13513
4. S. Yazji et al. J. Clin. Oncol. 2007, 24 (18, Suppl.), Abst 5094