|
The DNA in the vaccine codes for an altered form of the HPV's E7 protein, found in all HPV-16-infected tumor cells. The E7 protein is fused to a "heat-shock" protein, which helps boost the immune response by ferrying the E7 protein to the body's disease-fighting cells.
The vaccine will be used in at least three clinical trials at Hopkins in patients with preinvasive cervical cancer lesions or in patients with advanced head and neck cancer. Connie Trimble, M.D., assistant professor of obstetrics and gynecology at Johns Hopkins Medical Institutions, is the principal investigator on the cervical cancer vaccine trials. She and others designed a unique "pre-trial trial" to collect baseline data on the natural course of preinvasive cervical cancer lesions caused by HPV-16.
"We wanted to try and figure out what the natural immune response was to these lesions," said Trimble. The researchers collected tissue and lymphocytes over 15 weeks while monitoring the lesions. After 15 weeks, the women received state-of-the-art treatment. "People had never just watched in an organized way to see what would happen," she said, noting that while treatment would have been provided immediately if the lesions began to worsen, none worsened during the study period.
In fact, many women got better. "Thirty percent of the women resolved over 15 weeks, without any intervention," said Trimble. "So we started looking at the characteristics of lesions that resolve, and the characteristics of the women who resolve."
Women in the vaccine trial will receive three vaccinations four weeks apart, and will then be checked to see if the lesions have progressed. Seven weeks later, the women will receive standard treatment. "This study uses the same window [of time] as the previous study, so we'll be able to look at immune responses elicited by the vaccine and compare them to the natural immune responses," Trimble said.
"It's a unique situation because we can ask questions about what a successful immune response is against an established neoplastic process," she said. "That's the crux of the field of immunotherapy, but it isn't well understood in humans."
|
