BioWorld International Correspondent
LONDON - A vaccine designed to stimulate immune responses against a virus that is strongly linked to the development of several cancers has shown encouraging results in a small clinical trial.
The vaccine was tested on 18 women with a rare precancerous disease of the vulva, called vulval intraepithelial neoplasia (VIN). That is associated with the same form of human papillomavirus - HPV16 - that is strongly linked to cervical cancer.
VIN causes lesions on the skin of the vulva that can persist for decades, and that may eventually turn into cancer of the vulva. They can result in severe discomfort. Treatment with surgery is difficult, disfiguring and often of limited therapeutic benefit.
The trial, conducted at St Mary's Hospital in Manchester, UK, and funded by Xenova Research Ltd., of Cambridge, UK, showed that the experimental vaccine could shrink the lesions in almost half the women who were given it. Thirteen of the 18 women developed a specific immune reaction to HPV following vaccination, and in eight patients, the diameter of the lesions shrank by at least 50 percent. Another four patients experienced significant relief of symptoms.
A report of the study appears in the Sept. 10, 2003, Cancer Research in a paper titled "Immunological and clinical responses in women with vulval intraepithelial neoplasia vaccinated with a vaccinia virus encoding HPV 16/18 oncoproteins."
Peter Stern, head of the Cancer Research UK Immunology Group at the Paterson Institute, also in Manchester, told BioWorld International: "We were very pleased to see that giving this vaccine is associated with a clinical benefit in this group of women. The fact that we have obtained such encouraging results will also be useful in the wider field of cancer vaccines."
Stern said a further study already has begun in which women will be given a different vaccination schedule to try to stimulate even stronger immune responses.
The vaccine used is a vaccinia virus, genetically modified to carry the genes encoding proteins E6 and E7 of HPV. In the study reported in Cancer Research, women received a single dose of the vaccine. For the new study, participants will receive three vaccinations with a purified fused protein (which combines E6, E7 and an HPV capsid molecule called L2), followed by a booster of the genetically modified vaccinia - the so-called "prime-boost" technique.
"We hope to get even better results with this revised schedule," Stern said.
For the study published this month, the researchers also conducted a series of tests to assess whether the vaccine was stimulating an immune response. Thirteen of the 18 women showed some sort of increased immune response to HPV-16 at some point following immunization.
In six of eight of those whose lesions shrunk following administration of the vaccine, either viral load was reduced or the virus was cleared from the body. That also happened, however, in six out of the 10 women whose lesions did not shrink.
Tests also showed that those who responded clinically following vaccination had significantly higher levels of CD4, CD8 and CD1a immune cells in their lesions than those who had not responded clinically.
Stern said: "It has been suggested that vaccines work better in some patients than in others because there is a need for active immune cells or their products in the vicinity of a lesion. It could be that we'll need to test women beforehand, to identify a group who are most likely to benefit from vaccination."
One limitation of the published study, Stern said, was the fact that the trial was not placebo controlled. "In future trials we will need to try our vaccination schedule against some other type of treatment so that we can show whether it is better. Given the history of chronic disease in our patient group, however, where multiple previous treatments had been unsuccessful, spontaneous clinical improvement over a six-month period seems unlikely," he said.
In Cancer Research, team members record that several women in the study appeared to already have some immunity to vaccinia, probably because of previous smallpox vaccinations, although that was not specifically recorded. They wrote: "It is interesting to note that all six women with pre-existing vaccinia-specific T cells failed to show an objective clinical response over the course of the study. An explanation for this observation may be that vaccinia-specific T cells rapidly eliminate vaccinia-infected target cells and thus reduce the immunogenicity of the HPV vaccine, although previous clinical studies with this vaccine have not observed this effect."