Peregrine Pharmaceuticals Inc, a biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, has presented preclinical data at the 2008 Annual Meeting of the American Association for Cancer Research (AACR).
It shows that a mouse equivalent of Peregrine's anti-phosphatidylserine (anti-PS) vascular targeting antibody bavituximab administered in combination with the chemotherapeutic agent docetaxel demonstrated excellent signs of efficacy in a preclinical model of hormone-refractory prostate cancer. These new data confirm and extend the results of previous studies of Peregrine's anti-PS antibodies in models of prostate cancer. They were described by researchers in an oral presentation at the AACR Annual Meeting in San Diego, California.
Dr Yi Yin, a postdoctoral researcher in the laboratory of Dr Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center at Dallas, reported that in a mouse model of hormone-refractory prostate cancer, the combination of the bavituximab equivalent antibody 2aG4 and the chemotherapy drug docetaxel significantly decreased the growth of tumours, eliminated detectable metastases and prevented tumour re-growth. This increase in anti-tumour efficacy and anti-metastatic activity was achieved with no apparent increase in toxicity compared to docetaxel alone.
Specifically, in the study 2aG4 administered with docetaxel reduced primary tumour burden by 95 per cent, an anti-tumour effect that was significantly superior to that of the individual treatments administered alone. Treatment with the combination of 2aG4 and docetaxel also reduced the metastatic spread of tumour cells. In animals treated with the combination regimen, none of the treated mice (or 0%) exhibited detectable metastatic lesions, while 100 per cent of the mice treated with a non-specific control antibody, 67 per cent, of mice treated with 2aG4 alone and half the mice treated with docetaxel alone exhibited metastatic lesions. The combination was also superior at preventing tumour re-growth. Thirteen weeks post-treatment, tumours in animals treated with the combination regimen had regressed to less than 50 per cent, of their initial volume, while in mice treated with either therapy alone or with a control antibody, the tumours increased in size by factors of between 1.5 and 5 times. Survival time was more than doubled in animals receiving combination therapy compared to controls, and was substantially longer than the survival of animals treated with either therapy alone.
"These very promising results reinforce and extend the findings of previous preclinical studies highlighting the potential of our anti-PS antibodies in combination regimens for the treatment of prostate cancer," said Steven W. King, president and CEO of Peregrine. "We are particularly encouraged by data showing that the combination of a bavituximab equivalent and docetaxel eliminated the production of detectable metastases entirely in this model, while more than doubling the survival time of the treated animals. We are currently testing this same combination regimen of bavituximab and docetaxel in a phase II trial in patients with breast cancer, and we look forward to potentially assessing bavituximab in combination regimens in prostate cancer in future clinical trials".
Bavituximab is a monoclonal antibody that binds to a phospholipid called phosphatidylserine that is usually located inside normal cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumours, creating a specific target for anti-cancer treatments.
Prostate cancer is the most commonly diagnosed cancer in men, accounting for 30 per cent of all male cancers, and it is second only to lung cancer as a leading cause of cancer deaths in men. Currently, there is no cure for locally advanced or metastatic prostate cancer.
This research, which was conducted under the direction of Dr Thorpe at UT Southwestern, was supported in part by a sponsored research agreement with Peregrine Pharmaceuticals and by a grant from the US Department of Defense.