Researchers tap modified plant viruses to ward off cervical cancer-causing infections

New vaccinations to prevent infections that lead to cervical cancer and targeted therapeutics aimed at breast cancer were examples of research highlights presented by scientists today at the 95th Annual Meeting of the American Association for Cancer Research. Scientists described advances that feed into the drug development 'pipeline,' and show strong promise for controlling existing tumors or addressing the pathogen that causes tumors.

A novel pharmaceutical that inhibits progesterone receptor activity in breast cancer cells may reduce tumor mass in patients, according to scientists at Schering AG Corporate Research, Experimental Oncology based in Berlin, Germany.

Progesterone is a steroid hormone that activates its receptors in the nucleus of cells such as those found in the breast or uterus. In breast cancer cells, progesterone induces a cascade of biological events essential for cell proliferation. Proliferation leads to tumor development.

"It seems obvious that progesterone receptor antagonists could therefore block the growth of breast tumors that functionally express progesterone receptors," said Jens Hoffman, MS, Ph.D., the studies lead investigator.

Hoffmann and his colleagues from the Schering AG Corporate Research Business Area Oncology tested the new progesterone receptor antagonist in tumor cell models and observed strong antiproliferative activity. The progesterone receptor antagonist also prophylactically prevented the development of breast tumors following a chemical challenge designed to induce the growth of the breast tumors in rodent models.

"Our results revealed that the biological response to a progesterone antagonist does not seem to be only the result of competition of progesterone but rather may be accompanied by additional mechanisms," Hoffmann said. "The progesterone receptor antagonist appears to induce programmed cell death, or apoptosis."

In comparison to other therapeutics that target steroid receptors to reduce tumor growth, such as the anti-estrogen tamoxifen, the agent studied by Hoffmann and his colleagues is unique because it does not just stop the cell from growing and dividing; rather, it appears to prompt the cell to die.

"With the ability to trigger apoptosis in cancerous breast cells, this novel progesterone receptor antagonist may be a promising option for clinical breast cancer therapy or prevention," Hoffmann said.

Plant viruses show promise as carriers for new low-cost, antiviral vaccinations against human papillomaviruses (HPV) that cause benign and malignant tumors, according to research presented today.

A consortium of researchers from Large Scale Biology Corporation (LSBC), Vacaville, Calif., and the Department of Microbiology and Immunology, Penn State University College of Medicine developed the anti-HPV treatment by combining parts of papillomavirus structural proteins with the tobacco mosaic virus (TMV). Alison McCormick, Ph.D., Senior Scientist at LSBC, presented preliminary findings indicating that the virus-combining technology resulted in vaccinations that promoted antibody responses to rabbit papillomavirus types that are used as models for human papillomavirus disease, as well as to HPV strains associated with high risk for reproductive organ cancers.

HPV comprise a family of viruses that are often transmitted through sexual contact. While HPVs can cause genital warts, certain strains of the virus are known to induce cervical, vulvar and anal cancers, and are implicated in the development of other cancers including those to the head and neck. HPV is present in more than 9 of ten cases of all cervical cancers.

McCormick noted previous research demonstrated that virus-like particles from HPV proteins were very effective in generating an antibody response to a particular strain of the virus, but that it is unlikely that these vaccines would protect against all of the strains of HPV that cause human genital cancers. Furthermore, the technology to generate the virus-like particles posed expensive manufacturing challenges.

By incorporating the immunogenic peptides from papillomaviruses into the TMV virions, researchers at Large Scale Biology Corporation developed a relatively inexpensive, efficient technology to produce a viral antigen that generated strong peptide-specific immune responses in mouse models and antibodies capable of generating partial protective response in the cottontail rabbit model. McCormick and her colleagues are now performing research focused on improving these novel vaccines against papillomaviruses through research funded by the National Institutes of Standards and Technology's Advanced Technology Program.

"The key to preventing reproductive tract cancers caused by HPV is to block the initial infection," McCormick said. "Generating vaccines that protect against a wide array of HPV strains is a priority, since many different strains of HPV cause cancer. Without persistent viral infection, cancers caused by HPV are expected to fall in incidence."

Approximately 5,000 women die from cervical cancer each year in the United States. The Center for Disease Control and Prevention estimates that 5.5 million new cases of genital HPV occur yearly in the United States. As many as 24 million people in the U.S. are infected with HPV at any given time. An estimated 1 million women in the U.S. have cervical dysplasia associated with HPV, with 55,000 bearing in situ carcinomas. Approximately 15,000 U.S. women have cervical cancer.

Globally, HPV-induced cervical cancers are the most common cancers in women in developing countries. One half-million new cases of cervical cancer occur yearly across the globe, leading to 300,000 deaths. 80 percent of these occur in developing countries, and 90-95 percent are associated with HPV infection.

Control of the emerging worldwide health problem caused by HPV could best be accomplished through development of preventative and therapeutic vaccines against a wide variety of papillomavirus types. Ideally, these vaccines should be manufactured in abundant supply at a cost that is compatible with industrialized as well as developing world economies. LSBC's novel plant-virus-based system could offer one solution to this growing medical and public health need.