From rxpgnews.com

Vaccination
A Vaccine For Carcinoma Cervix
By University of Rochester Medical Center, Mar 4, 2005 - 10:05:38 AM

A vaccine to prevent a type of cancer that kills more than 250,000 women around the globe every year is expected to become available within a year or two, thanks in large part to technology developed by scientists at the University of Rochester Medical Center.

Vaccines that prevent cervical cancer are in the final stages of testing in studies by two companies, Merck and Co. and GlaxoSmithKline (GSK). Earlier this month the two pharmaceutical giants agreed on a settlement involving patents and royalties related to the vaccines, clearing the way for continued development of their products.

The vaccine targets a group of viruses known as human papillomaviruses (HPV), which cause 12,000 cases of cervical cancer in women in the United States annually. About 4,500 women in the nation die of the disease every year. The toll is much worse in other parts of the world, where Pap smears to detect the disease in its earliest stages are not widely available. In some parts of the world, cervical cancer is the leading cause of death by cancer in women.

Research done more than a decade ago by a trio of University virologists – Richard Reichman, M.D., William Bonnez, M.D., and Robert Rose, Ph.D. – is integral to the technology, which takes aim at a portion of a class of viruses that also cause all warts.

A patent application was filed, and the rights to the technology were licensed to the biotechnology company MedImmune, which then sold the license to SmithKline (which later became GSK). Now, the research is poised to save lives and become part of one of the first vaccines to prevent a form of cancer. (The hepatitis B vaccine can also prevent liver cancer.)

“The public health impact of this work – which has the potential to prevent a condition that causes significant morbidity and mortality in women – is enormous, both nationally and internationally,” says David Guzick, M.D., Ph.D., dean of the School of Medicine and Dentistry and professor of Obstetrics and Gynecology.

Pretty much everyone has encountered an HPV in one form or another. There are more than 100 types of HPV. Some cause common warts on the hands or plantar warts on the feet. At least 40 types of HPV infect the genital tract, causing warts in some people and a variety of other conditions, most notably cervical cancer and other cancers in women, anal cancer in men and women, and occasionally penile cancer in men.

In the United States, more than 15,000 people every day, or about 5.5 million people a year, get sexually transmitted HPV infections from their partners. About three out of every four sexually active people will get an HPV infection at some point during their lifetime; in some age groups, such as sexually active men and women under the age of 30, doctors estimate that 40 percent of people are currently infected.

Most people fight off the virus and never even know they were infected. Others have warts. In the most serious cases, in about 1 percent of women with the virus, it progresses to abnormal cell growth known as dysplasia and sometimes to cervical cancer. Two types of HPV, type 16 and type 18, cause about 70 percent of cervical cancers, and those are the types that the two current vaccines in development are designed to prevent.

Scientists have published results in the Lancet and New England Journal of Medicine that show that both vaccines protect against those two types of HPV, and now both vaccines are being studied in larger studies involving tens of thousands of women. The vaccines are given as a series of three shots given a few months apart.

Scientists and public health officials are discussing who should receive the vaccine, and when; most doctors say the vaccine would need to be given before a person becomes sexually active to do the most good. Women have the most to gain from protection against HPV, while men who were protected may be much less likely to spread the disease.

The key to the technology is VLPs, or virus-like particles, which have become VIPs in the world of infectious disease. Twenty years ago the team set out on a basic research study to look at how a person’s immune system fights HPV infection. The team soon focused on the actual viral particle that causes the disease.

After discovering that the body produces antibodies that could neutralize the virus, they figured out how to make harmless virus-like particles to trigger the same immune response. They did this by putting an HPV gene into insect cells using a virus called baculovirus, which infects insects; the HPV gene then produces particles that mimic the shape of real HPV particles.

Each member found his way to Rochester and the field of HPV for his own reasons. Reichman, director of the Infectious Diseases Unit, was an expert on sexually transmitted viral diseases and took the advice of a visiting senior colleague that human papillomaviruses offered a good research opportunity.

Bonnez, a classically trained virologist, came to the United States from France largely for the opportunity to do research on viruses while still treating patients. And as a graduate student, Rose sought an opportunity to study viruses and their structure in a way that would have an impact on human health.

“The medical center was able to bring together individuals from disparate backgrounds who have this common link, an interest in science as a vehicle to improve the health of populations. This extraordinary achievement, in which basic science discoveries are translated into clinical and public health practice, is the essence of what an academic medical center is all about,” says Guzick.

With VLPs in hand, the team promptly filed for a patent and in early 1997 began one of the world’s first tests in humans of a vaccine to prevent HPV infection. That study of 65 people found that the vaccine was safe and provokes an immune response in people and prompted further studies, culminating in a promising product for GSK. Like any vaccine, the products are designed to trigger an immune response, so that if the person encounters the disease, the body is primed to fight it off.

Marjorie Hunter, director of the medical center’s Office of Technology Transfer, led recent negotiations that have helped iron out the intellectual property agreements. A previous technology transfer director, Robert Goodwin, helped link the researchers with MedImmune in 1995, a key step in keeping the technology alive. Also important was the consistent support and dogged determination of Michael Goldman of the Rochester law firm Nixon Peabody, who filed the initial patent.

Reichman, Rose and Bonnez continue to do research on HPV and other diseases. Reichman is investigating cervical HPV disease in women infected with HIV; Rose focuses on development of needle-free methods for delivery of the vaccine in developing countries; and Bonnez pursues his interests in defining exactly how the virus causes disease. In addition, Rose and Bonnez are members of a large team of investigators led by Tim Mosmann, Ph.D., director of the Center for Vaccine Biology and Immunology, who are looking at how and why the immune system naturally fights off HPV in some people but not in others.

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