Data Presented at AACR Meeting Show Peregrine`s Bavituximab Equivalent Can Generate Curative Immune Responses as Part of a Vaccine-Like Regimen in Preclinical Models of Aggressive Brain Cancer
Posted on: 04/18/2007
Data Presented at AACR Meeting Show Peregrine's Bavituximab Equivalent Can Generate Curative Immune Responses as Part of a Vaccine-Like Regimen in Preclinical Models of Aggressive Brain Cancer
Posted : Wed, 18 Apr 2007 13:48:00 GMT
Author : Peregrine Pharmaceuticals, Inc.
Category : PressRelease
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LOS ANGELES and TUSTIN, Calif., April 18 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. , a clinical stage biopharmaceutical company developing targeted monoclonal antibodies for the treatment of cancer and hepatitis C virus (HCV) infection, today announced preclinical studies presented at the Centennial Annual Meeting of the American Association for Cancer Research (AACR) showed that 2aG4, a mouse equivalent to the company's anti-phosphatidylserine (PS) antibody bavituximab has vaccine- like activity and can generate curative responses in an aggressive model of brain cancer. Researchers also presented data demonstrating that this improvement in survival was likely attributable to the ability of 2aG4 to enable the treated animals to mount an effective immune response against this difficult to treat cancer.
To confirm that the bavituximab equivalent 2aG4 acted by enhancing anti- cancer immune responses, researchers injected rats with irradiated glioma cells (inactivated tumor cells) along with 2aG4. This regimen was intended to protect the animals from a subsequent challenge with a large lethal dose of tumor cells -- 10,000 times the number required to produce lethal disease in this model.
Among the animals pre-treated with the 2aG4-treated irradiated cells, 57% achieved long-term survival, versus 0% of animals receiving no prior treatment (P < 0.01). The key role of the bavituximab equivalent's anti-PS activity in protecting these animals was illustrated by the fact that a group receiving irradiated control antibodies that did not block PS only achieved a 16% long- term survival rate.
These data are particularly noteworthy because the glioma cells used in the study are highly aggressive -- fewer than 10 cells can fuel development of a lethal tumor. In addition, the researchers calculated that in order to achieve the long-term survival observed in the animals receiving the 2aG4 regimen, more than 99.99% of the glioma cells contained in the challenge dose would have had to have been destroyed by the immune system. These results indicate that the 2aG4 vaccine-like regimen resulted in a strong immune response to the cancer not seen in controls.
"These exciting data suggest a potential new application for bavituximab and our anti-PS antibody platform as part of a cancer vaccine regimen that aims to restore the ability of the patient's own immune system to recognize and fight cancer," said Steven W. King, president and CEO of Peregrine. "Based on these promising results, we are continuing our evaluation of these vaccine-like regimens containing bavituximab for potential application to a variety of cancers."
Study data further showed that administering the combination of 2aG4 and irradiated tumor cells to the glioma cell-challenged animals resulted in a robust immune response, including enhanced cross-presentation of tumor antigens, increased expression of inflammatory anti-cancer cytokines and enhanced recognition and phagocytosis of tumor cells by macrophages. A key result was the fact that inclusion of the bavituximab equivalent in the regimen appeared to reverse suppression by tumor cells of the ability of dendritic cells to "present" cancer cells for destruction by the immune system. In these studies, the animals receiving 2aG4-treated irradiated cells showed increased antigen presentation of PS positive tumor cells by dendritic cells, as well as an increase in the number of cytotoxic T cells enabling the animals' immune systems to attack the tumor cells directly. These results are key signs of a strong immune response.
"We believe that a key mechanism of action of our anti-PS agents is that they block the immune-suppressing effects of phosphatidylserine in conditions such as cancer," said Dr. Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center and a member of the Peregrine Scientific Resource Board. "These new studies in animal models of aggressive brain cancer are the strongest evidence yet that this is the case. We are eager to explore further the promising immune-enhancing activity demonstrated by our anti-PS antibody against this lethal cancer."
Bavituximab is a targeted monoclonal antibody that binds to a phospholipid called phosphatidylserine (PS), which is normally located on the inside of cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors. Once bound to tumor blood vessels, bavituximab alerts the body's immune system to attack the tumor's blood supply, stopping the flow of oxygen and nutrients to the tumor cells and resulting in tumor cell death. PS is also thought to play a role in suppressing the body's immune response to cancer. PS blockers may have the potential to help reverse this suppression and enable the immune system to attack the cancer more effectively. As an anti-cancer immunotherapeutic, bavituximab may have broad potential in a wide variety of solid cancers. It is currently in Phase Ia cancer safety trials as a monotherapy and in a Phase Ib trial in combination with docetaxel and other chemotherapy agents in patients with advanced solid cancers, including prostate, breast and lung cancer. Based on interim data, more than half of the cancer patients in this study who have completed treatment to date were assessed as demonstrating stable disease or an objective response.
This research was conducted under the direction of Dr. Thorpe and postdoctoral researcher Dr. Jin He at UT Southwestern Medical Center in Dallas.
This work was supported in part by the Meredith C. Chestler Foundation, the Childhood Brain Cancer Foundation and the Gillson Longenbaugh Foundation and by a sponsored research agreement with Peregrine Pharmaceuticals Inc.
Number 4091: Enhancing the immunogenicity of glioma cells with anti- phosphatidylserine antibody, Jin He, Troy A. Luster, Philip E. Thorpe. UT Southwestern Medical Center, Dallas, TX, Apr 17, 2007, 8:00 AM - 12:00 PM EDT
About Peregrine Pharmaceuticals
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that pre-clinical animal model efficacy results will not correlate to efficacy studies in human clinical trials, the risk that future studies will not support a potential role for anti-PS therapies, such as bavituximab, as an immune-enhancing cancer vaccine, and the risk that future studies may not support the initiation of human clinical trials. It is important to note that the company's actual results could differ materially from those in any such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the Company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2006 and the quarterly report on Form 10-Q for the quarter ended January 31, 2007. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release
Peregrine Pharmaceuticals, Inc.
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