TAMPA An experimental vaccine against human papillomavirus appeared to have therapeutic potential in a study of 20 women with HPV-16 positive vulvar intraepithelial neoplasia.
Treatment with the vaccine resulted in important T-cell responses in most patients after two vaccinations in the phase II study of women with histologically proven vulvar intraepithelial neoplasia (VIN). At 3 months, clinical efficacy was apparent in more than 50% of patients, and a complete response occurred in 25%, Dr. Gemma G. Kenter reported at the annual meeting of the Society of Gynecologic Oncologists.
The vaccine's design is based on long, overlapping peptides that cover the complete amino acid sequence of the HPV-16 E6 and E7 oncogenic proteins. Patients in the study were vaccinated four times at 3-week intervals. Interferon-gamma enzyme-linked immunospot (ELISPOT) analysis indicated that nearly all of the patients mounted a T-cell response to multiple regions of HPV-16 E6, and 75% did so against HPV-16 E7. These oncogenes represent the best targets for therapeutic vaccination, said Dr. Kenter of Leiden University (the Netherlands) Medical Center.
The natural HPV-specific E6 and E7 immune response is different in healthy patients than in infected patients, and proliferation assays in this study showed that the T-cell reactivity that was demonstrated is associated with the production of IFN-gamma and interleukin-5, similar to the cytokine profile of the HPV-16-specific memory T-cell responses observed in healthy individuals, Dr. Kenter explained.
A local immune response, namely infiltration of both the vaccination site and/or the VIN lesion by HPV-16-specific Th1 and Th2 cells, also was demonstrated.
The findings are encouraging, because HPV infection is common in young, sexually active individuals, and although most will clear the infection without developing clinical disease, some people experience a failure of the immune system in controlling the virus, and in these patients, malignancy can develop. The current study followed a phase I study in which the vaccine was found to elicit a strong HPV-16-specific T-cell response in 35 patients with end-stage cervical cancer, with no toxicity greater than grade 2 occurring.
"To our surprise, even in this patient group with end-stage disease, vaccination induced a strong type I immune response," Dr. Kenter said. A response to the E6 oncogene occurred in 90% of the patients, and a response to E7 occurred in 70%.