Network - Spring 2013
Cancer vaccines self-sabotage, channel immune attack to injection site
Cancer vaccines that attempt to stimulate an immune system assault fail because the killer T cells aimed at tumors find the vaccination site a more inviting target, scientists at MD Anderson report in Nature Medicine.
A common substance used in many cancer vaccines to boost immune attack encourages a buildup of T cells at the vaccination site, which then summon more T cells to help with the perceived threat.
The result is largely unscathed tumors while an overstimulated immune response can cause lesions at the injection site.
The team found that a major culprit in this failure is incomplete Freund’s adjuvant (IFA), a mineral oil-based adjuvant included in many vaccines to stoke the immune response. Eventually, the T cells die.
“But switching to a saline-based adjuvant in a melanoma vaccine reversed the T cell effect in mice,” says senior author Willem Overwijk, Ph.D., associate professor in the Department of Melanoma Medical Oncology.
“Major accumulations of T cells gathered in tumors, shrinking them, with minimal T cell activity at the vaccination site.”
The hope is that a saline adjuvant could change the poor performance of cancer vaccines. A clinical trial of the concept is expected to open later this year at the University of Virginia and MD Anderson.
Drug is first to control recurrent low-grade ovarian cancerA Phase II clinical trial of a targeted therapy provides evidence that there might, at last, be a treatment that shrinks or stifles the growth of recurrent low-grade serous ovarian cancer.
Women with low-grade disease tend to be younger and survive longer than those with high-grade ovarian cancer, but when their cancer persists or comes back, it almost always thwarts treatment. Between 2% and 4% of patients respond to chemotherapy. Hormonal therapies do modestly better, with a 9% response rate.
In the clinical trial of the drug selumetinib published in the February edition of The Lancet Oncology, eight of 52 (15%) patients had a complete or objective partial response (tumor shrinkage) and 34 (65%) had no disease progression during the two-year study.
Cancer-causing genetic mutations in BRAF and KRAS genes occur more frequently in low-grade ovarian cancer, so the researchers chose a drug that targets the molecular network that includes those genes.
Selumetinib inhibits MEK1/2, a critical molecule in what’s known as the MAPK pathway, which includes BRAF and KRAS.
“These are remarkably encouraging results for what can ultimately be a devastating disease,” says senior author David Gershenson, M.D., professor in MD Anderson’s Department of Gynecologic Oncology and Reproductive Medicine.