AACR Annual Meeting Coverage

HPV Vaccines Demonstrate Long-Term Protection
New data presented at the AACR annual meeting today on the longer term effectiveness of two human papillomavirus (HPV) vaccines demonstrate strong protection against the two HPV types linked to more than 70 percent of cervical cancers as well as the precancerous lesions associated with them.

Data from the ongoing evaluation of participants in a phase II trial testing a still-experimental vaccine manufactured by GlaxoSmithKline (GSK) called Cervarix showed that more than 98 percent of the 776 participants for whom extended follow-up data are available maintained protection against HPV types 16 and 18 - considered the two most oncogenic HPV types - for more than 5 years.

The vaccine, reported the study's lead investigator, Dr. Stanley Gall from the University of Louisville, provided near complete protection against HPV types 16 and 18 incident infection (98 percent), 100-percent protection against 6- and 12-month persistent infection, and protection against most instances of HPV-associated precancerous growths. Although it's only designed to protect against HPV types 16 and 18, the GSK vaccine also demonstrated protection against incident infections of HPV type 45 (88 percent) and HPV type 31 (54 percent), which together account for approximately 10 percent of cervical cancers, Dr. Gall explained.

GSK applied to the FDA for marketing approval for Cervarix on March 29.

Longer term data also were presented on more than 12,000 women in a phase III trial testing Gardasil, the HPV vaccine approved by the FDA last year. Dr. Darron Brown of the Indiana University School of Medicine reported that, 3 years after completion of the three-shot vaccine regimen, Gardasil provided virtually complete protection against precancerous lesions associated with HPV types 16 and 18, and HPV 16 and 18 antibody levels continue to be significantly elevated.

In the 241 women for whom 5-year follow-up data are available, Dr. Brown reported, Gardasil provided 100-percent protection against HPV 16- and 18-related precancerous lesions. A preplanned substudy of vaccine cross-protection against other HPV types has been completed, Dr. Brown added. Although the final results are not ready for presentation, he said, the available data are "very encouraging."

Engineered Virus Delivers Killer Protein to Prostate Cancer Cells
Researchers from Columbia University have developed a novel gene therapy technique that uses a virus engineered to replicate only within cancer cells and produce a protein toxic to those cells. The results of their laboratory studies, presented at the 2007 AACR annual meeting, showed complete eradication of both primary and distant tumors in a mouse model of prostate cancer.

The investigators built their system around a gene called mda-7/IL-24, which produces the cytokine IL-24, a signaling protein important to the immune response, that kills cancer cells when expressed at high levels. They engineered an adenovirus carrier for the gene, which can multiply within cancer cells. The virus was altered to replicate in response to transcription factors found only in cancer cells. When the virus enters a cancer cell, the researchers explained, it replicates millions of copies of itself and produces IL-24, which kills the cell and releases a flood of virus into the bloodstream to infect and kill other cancer cells.

After in vitro experiments confirmed that viral replication was confined to cancer cells and induced growth inhibition and cell death, the investigators tested their gene therapy system in a xenograft mouse model of therapy-resistant prostate cancer. The virus completely eradicated not only the primary tumor but also distant tumors, explained the study's leader, Dr. Devanand Sarkar from Columbia University.

An earlier version of the therapy has already been tested in a phase I clinical trial, producing a significant clinical response in several of the patients who completed one 28-day treatment cycle. Experiments to test the next-generation treatment in mice with fully functional immune systems are ongoing, Dr. Sarkar said.

Risk of Colon Cancer in African Americans Linked to Genetic Variants
Any one of four DNA variants in a gene involved in mediating inflammation may significantly increase the risk of colon cancer in African Americans, according to the results of an ongoing study presented at the AACR annual meeting. The risk is even further heightened in African American men who have two copies of all four variants, the research team found.

The finding may provide some insight into the higher colon cancer incidence and mortality in African Americans seen over the past three decades when compared with Caucasians, according to Dr. Krista A. Zanetti, a Cancer Prevention Fellow, and Dr. Curtis C. Harris, chief of the Laboratory of Human Carcinogenesis in NCI's Center for Cancer Research (CCR).

Despite the small sample size of African American cases and controls, "These results are particularly robust," Dr. Zanetti said. The variants are single nucleotide polymorphisms (SNPs), which are places in the genome where a single unit of DNA may vary from one person to the next.

The team conducted a case-control study that included 261 individuals with colon cancer and 537 healthy individuals, all from the greater Baltimore area. Of these, African Americans represented 103 cases and 201 controls. In African Americans, four SNPs in the MBL2 gene increased the risk of colon cancer at least three- to fourfold compared with African Americans without the genetic variants. In African Americans with two copies of all four MBL2 variants, there was a nearly sixfold increased risk. These associations were not seen in Caucasians.

Additional studies are needed to clarify and validate these findings, Dr. Zanetti explained.

"Given the lower frequency of these SNPs in Caucasians than African Americans in this study, we may need a larger number of samples to see if this association exists in Caucasians as well," Dr. Zanetti said. They are investigating this by using case and control samples from the ongoing, NCI-funded Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.