Business Wire - October 1, 2002
Until now, the instability of these surface "spikes" has hampered efforts to produce an effective prophylactic vaccine. The new vaccine components are designed to elicit an immune response capable of neutralizing the human immunodeficiency virus (HIV), the virus that causes AIDS, before it can establish infection. The findings were described in two recent articles in the Journal of Virology.
"Our new vaccine candidates are the culmination of several years of effort to first determine, and then mimic as closely as possible, the native form of the HIV envelope spike - the glycoproteins which protrude from the virus," said John P. Moore, Ph.D., Professor of Microbiology and Immunology at the Weill Medical College of Cornell University, and senior author of the Journal of Virology publications. "The rationally designed envelope trimers described in these studies more faithfully resemble the structures on the virus surface than proteins that have been made previously, so they may prove to be more effective vaccine candidates."
"The production of stable envelope trimers represents an important step towards our goal of developing a vaccine that protects individuals from becoming infected with the virus," said Paul J. Maddon, M.D., Ph.D., Progenics' Chairman and CEO. "We have begun testing these trimeric constructs in animals to determine their ability to elicit antibodies capable of neutralizing naturally occurring strains of HIV. Success in the animal studies would support advancement of our vaccine candidates into human clinical trials."
Prophylactic HIV vaccines, which are under development by companies and academic laboratories worldwide, are designed to work by eliciting antibodies that target viral surface proteins and neutralize the virus. The surface of HIV is studded with envelope spikes that consist of three copies each of the gp120 and gp41 glycoproteins in a trimeric configuration. These envelope trimers mediate entry of the virus into immune system cells. Blocking this viral-entry process thus impedes infection. However, the instability of the natural form of the timer complex in the laboratory has been a major obstacle to the creation of a vaccine, as the dissociated components, monomeric gp120 and gp41, do not reliably elicit antibodies that neutralize circulating strains of HIV.
The Journal of Virology papers co-authored by researchers at Progenics and Cornell (76(15) 7760-7776 and 76(17) 8875-8889) describe two novel strategies for producing the stabilized gp120/gp41 proteins in their native trimeric form. The first approach involved modifying the gp120 glycoprotein to enhance trimer stability, whereas the second method employed modifications to gp41. Importantly, the trimers can be isolated in homogenous form, as required for use in a vaccine. The collaborating scientists believe that a vaccine containing the trimeric structure of HIV surface proteins may be crucial to eliciting a immune response able to neutralize the virus in humans.
"An effective HIV vaccine offers the greatest potential for stemming the worldwide spread of AIDS," said Dennis R. Burton, Ph.D., Professor of Immunology at The Scripps Research Institute in La Jolla, CA, and a leading expert in the area of HIV vaccine research. "Vaccines against other viruses work by generating antibodies that bind the surface of the virus, thereby rendering it non-infectious. However, such neutralizing antibodies to HIV have been difficult to induce with vaccines currently in development. The new viral envelope trimers represent very interesting leads for HIV vaccine development."
Progenics Pharmaceuticals, Inc. of Tarrytown, NY, is a diversified biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. The Company applies its expertise in immunology and molecular biology to develop biopharmaceuticals to fight viral diseases, such as human immunodeficiency virus (HIV) infection, and cancers, including malignant melanoma and prostate cancer. In supportive care, therapies are being developed to provide patients with an improved quality of life. The Company is conducting Phase II clinical studies with methylnaltrexone, a compound designed to block the debilitating side effects of opioid analgesics without interfering with pain palliation. The Company has initiated Phase II clinical trials with its lead HIV product, PRO 542, a viral-entry inhibitor and is in preclinical development with PRO 140 and other follow-on product candidates in HIV infection. Progenics' most clinically advanced product, GMK, is a cancer vaccine in Phase III clinical trials for the treatment of malignant melanoma. The Company is developing cancer immunotherapies based on PSMA (prostate specific membrane antigen) technology. Dehydroascorbic acid (DHA), a novel small-molecule antioxidant, is the subject of preclinical studies to treat stroke.
This press release contains forward-looking statements. Any statements contained herein that are not statements of historical fact may be forward-looking statements. When the Company uses the words 'anticipates', 'plans', 'expects' and similar expressions they are identifying forward-looking statements. Such forward-looking statements involve risks and uncertainties which may cause the Company's actual results, performance or achievements to be materially different from those expressed or implied by forward-looking statements. Such factors include, among others, the uncertainties associated with product development, the risk that clinical trials will not commence when or proceed as planned, the risks and uncertainties associated with dependence upon the actions of the Company's corporate, academic and other collaborators and of government regulatory agencies, the risk that products that appear promising in early clinical trials do not demonstrate efficacy in larger-scale clinical trials, the uncertainty of future profitability and other factors set forth more fully in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2001 and other periodic filings with the Securities and Exchange Commission to which investors are referred for further information. In particular, the Company cannot assure you that any of the their programs will result in a commercial product. The Company does not have a policy of updating or revising forward-looking statements, and thus it should not be assumed that the Company's silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements.
Editor's Note: Additional information on Progenics is available at http://www.progenics.com
CONTACT: Progenics Pharmaceuticals, Inc. Richard W. Krawiec, Ph.D., 914/789-2800 Vice President Investor Relations and Corporate Communications rkrawiec@progenics.com
SOURCE: Progenics Pharmaceuticals, Inc.
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