Treatment might stop cancers before they arise
Three shots in the arm can awaken the immune system to home in on aberrant growths on the cervix, potentially derailing cancer in the making. When given to 12 women with the precancerous condition, the injections triggered the homegrown attack and wiped out wayward cells in a matter of weeks in five of the patients, scientists report in the Jan. 29 Science Translational Medicine.
The study joins a small body of research showing that immunotherapy can gain traction against cancer or premalignant growths. This approach is sometimes described as a “cancer vaccine,” but that term is slightly misleading. Immunotherapy enlists the immune system as a vaccine does, but to treat a disease, not prevent it. In this case, the immunotherapy includes a mix of proteins, genes and a virus. The combination guides immune cells like a searchlight to deranged, precancerous cells that have been commandeered by the human papillomavirus.
The immune system normally clears most HPV infections on its own. But sometimes the virus evades detection. In so doing, it can infiltrate genital or mouth tissues and set cells on an aberrant growth path by installing its genes into a cell’s DNA. The viral genes trick the cell into making a troublesome pair of proteins called E6 and E7, which sabotage the cell’s tumor suppressing machinery.
The experimental immunotherapy includes a weakened version of a poxvirus toting HPV genes that encode modified versions of E6 and E7. It also contains proteins activated by stress and other ingredients, all designed to grab the immune system’s attention. The immunotherapy differs from HPV vaccines aimed at preteens and teens, which prevent initial infection but don’t seem to work in people already carrying the sexually transmitted virus.
In the study, researchers chose 12 women who had been diagnosed with advanced precancerous lesions on the cervix. Each woman received three immunotherapy injections over eight weeks. Seven weeks after the final shot, doctors surgically removed the cervical tissue from the lesion site as well as small portions of healthy nearby tissue.
In five women, no sign of the lesions remained. Two of the other women showed considerable improvement. An analysis of tissues under the microscope revealed an immune onslaught of cells and proteins at the lesion site but not in healthy tissue. Even tissue samples from the remaining five women, who showed less improvement, were “crawling” with immune cells, says study coauthor Cornelia Trimble, a gynecologic pathologist at the Johns Hopkins Medical Institutions in Baltimore.
The findings indicate a localized immune assault, she says. Blood drawn elsewhere in the body showed little immune reaction to the shots. The researchers say this might explain in part why previous “cancer vaccines” have seemed to help some patients even though their blood showed no clear signs of immune mobilization.
The lesions were removed 15 weeks after the first shot, Trimble says, so whether the immunotherapy would have continued to clear precancerous cells beyond that point still needs to be determined.
Gemma Kenter, a gynecologist at the University of Amsterdam, says the immunotherapy approach might also work on HPV-caused vulvar lesions, which are less common than cervical growths but can be harder to treat. She notes that genital precancerous lesions caused by HPV recur in 5 to 10 percent of women who have either cleared them naturally or have had them removed. Adding the immunotherapy, she says, “might be ideal for the small percentage of women who have insufficient success from surgery.”
L. Maldonado et al. Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Science Translational Medicine. Vol. 6, January 29, 2014. doi: 10.1126/scitranslmed.3007323.
G. G. Kenter et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. New England Journal of Medicine. Vol. 361, November 5, 2009, p. 1838. doi: 10.1056/NEJMoa0810097.
S. Daayana et al. Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. British Journal of Cancer. Vol. 102, March 16, 2010, p. 1129. doi:10.1038/sj.bjc.6605611.
N. Seppa. Dose of Reality: HPV is epidemic, which is odd since it is largely preventable. Science News. Vol. 183, April 20, 2013, p. 20.
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