According to a phase IIb clinical trial, an investigational DNA vaccine that targets the human papillomavirus caused precancerous cervical lesions to regress or disappear. The vaccine stimulated production of CD8+ T cells that make perforin, a protein that helps kill infected cervical cells, and eliminated the virus in 81% of women whose lesions regressed.

A DNA vaccine that targets strains of the human papillomavirus (HPV) causes cervical lesions to regress or disappear, a phase IIb trial shows.

In most women who are infected with HPV, the immune system attacks and eliminates the virus. The two approved HPV vaccines, Gardasil and Cervarix, help protect against new infections with HPV-16 and HPV-18, the strains responsible for 70% of cervical cancers, but they don't clear the virus from already-infected patients. HPV infection can trigger a precancerous lesion known as cervical intraepithelial neoplasia (CIN).

Doctors can't predict which lesions will progress to cervical cancer, so the standard treatment is to have them excised. However, more than one procedure is often necessary, and deep excisions can increase the risk of premature birth. Researchers are working on several less invasive alternatives, including therapeutic vaccines, to induce immune responses that would eliminate HPV.

Cornelia Trimble, MD, of the Johns Hopkins School of Medicine in Baltimore, MD, and colleagues tested an investigational therapeutic DNA vaccine, VGX-3100, developed by Inovio Pharmaceuticals (Plymouth Meeting, PA). VGX-3100 contains plasmids that target two key HPV proteins, E6 and E7. After receiving a dose of the vaccine, which is injected into the arm, patients receive a mild electrical pulse at the injection site. This increases the permeability of the cell membrane, allowing cells to absorb the plasmids.

Trimble and colleagues reported the results of a trial of the vaccine in women with CIN2 or CIN3 lesions (Lancet 2015 Sep 16 [Epub ahead of print]). In 49.5% of the 107 women who received all three planned doses of the vaccine, the lesions vanished or regressed. In contrast, lesions disappeared or regressed in 30.6% of the 36 women who received three placebo injections. In these patients, the immune system attacked HPV without stimulation from the vaccine.

The scientists also confirmed that the vaccine triggered a response by the immune system. Compared with the control group, patients who received VGX-3100 produced more HPV-targeting CD8+ T cells that make perforin, a protein that helps kill infected cervical cells. In addition, 81% of the vaccinated women whose CINs regressed showed no trace of the virus, versus 45% of the subjects who received the placebo. “The study proves that it's possible to produce a T-cell response in people with existing disease, and that this T-cell response works,” says Trimble.

“The amount of viral clearance they had in this study was quite impressive,” says Henry Kitchener, MD, of the University of Manchester in the United Kingdom, who wasn't connected to the research. Eliminating the virus is crucial, he says, because “if you don't clear the virus, it's highly likely [the lesions] will recur” and cancer could develop. Kitchener adds that he wants to see long-term studies to confirm that the lesions don't return.

Trimble notes that VGX-3100 isn't as effective as surgery, which can eliminate the lesions in up to 90% of patients. That's why the researchers are working to increase its ability to stimulate the immune system.

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