New HPV vaccine eliminates chronic infection and reduces precancerous genital lesions in women

A new vaccine designed to stimulate an immune response against a cancer-causing human papillomavirus (HPV-16) can eliminate chronic infection by the virus and may cause regression of precancerous genital lesions in women who receive the vaccine.

According to a report published in the November 5 issue of the New England Journal of Medicine (2009;361:1838-47), the vaccine successfully induced HPV-specific immune responses in 100% of patients with advanced vulvar intraepithelial neoplasia (VIN3), a life-threatening disease that in the majority of cases results from HPV infection and for which there is as yet no satisfactory standard therapy.

Among the women who participated in the study, the majority (79%) experienced measurable regression of their VIN3 lesions within 1 year of vaccination. Nine of the women (47%) experienced complete disappearance of lesions and were still symptom-free two years following vaccination. The virus was undetectable in four of five women whose disease had regressed completely after the first year.

According to researchers who conducted the phase II study at the Leiden University Medical Center in Leiden, The Netherlands, spontaneous regression of HPV-16 positive VIN3 lesions is very rare, occurring in less than 1.5% of patients. The induction of HPV-specific T-cell immune responses following vaccination, and the researchers' observation that stronger vaccine-induced immune responses correlated with better clinical outcome indicate that the vaccine is the most likely cause of the high response rate among the patients treated in the study.

Unlike recently approved vaccines that prevent against infection by HPV, such as Merck's Gardasil® and GlaxoSmithKline's Cervarix®, this is a therapeutic HPV vaccine for people who have already been exposed to HPV and who are unable to clear the virus on their own and are at high risk of developing HPV-related cancer.

The vaccine is composed of HPV synthetic long peptides (SLP®), a proprietary technology developed by Dr. Cornelis Melief and others at Leiden University in The Netherlands in partnership with ISA Pharmaceuticals. In recognition of this and his other important contributions to the development of immune-based therapies for cancer, Dr. Melief received in June of this year the 2009 William B. Coley Award for Distinguished Research in Tumor Immunology from the Cancer Research Institute (CRI), a nonprofit organization based in the United States dedicated exclusively to harnessing the power of the immune system to treat, control, and prevent cancer.

To accelerate the testing and refinement of synthetic long peptides in the treatment of cancers that are not of viral origin, the Cancer Research Institute awarded Dr. Melief a grant of $300,000 for the establishment of a Good Manufacturing Practice (GMP) facility at Leiden University. The facility will produce clinic-grade synthetic long peptides for use in clinical trials within the Cancer Vaccine Collaborative (CVC), a joint program of the Cancer Research Institute and the Ludwig Institute for Cancer Research Ltd (LICR) in 2009.

The CVC is a global network of academic clinical trial sites and immune monitoring laboratories that is carrying out a coordinated program of early stage trials of therapeutic cancer vaccines. To date, the CVC has conducted more than 40 trials of various combinations of therapeutic vaccines targeting highly immunogenic cancer antigens, chiefly the NY-ESO-1 antigen. NY-ESO-1 is a prototypic member of the cancer-testis (CT) family of antigens, which are expressed in cancer but not normal adult tissue. In a recent publication, the National Cancer Institute prioritized this antigen among the top 10 most promising cancer immunotherapy targets available. NY-ESO-1 has been the central focus of CVC and other CRI or LICR sponsored studies for more than a decade.

Dr. Melief will supply CVC investigators with synthetic long peptides derived from XAGE antigens, which have properties similar to other CT antigens including NY-ESO-1. XAGE antigens are expressed in a number of cancers, particularly adenocarcinoma of the lung. CVC investigators will test the efficacy of delivering XAGE in the form of synthetic long peptide as compared to vaccines that deliver XAGE in the form of whole protein or DNA.

Upon completion of the GMP upgrade to Leiden University's synthetic long peptide production facility, it will be the second of two academically funded and operated bioproduction facilities within the CVC network. The first, at Cornell University in Ithaca, New York, recently completed production of clinic-grade recombinant NY-ESO-1 protein for CVC trials in melanoma and ovarian cancer, and is now producing clinic grade Melan-A/MART-1 protein for CVC clinical trials.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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