Roswellness August 2007 - Online Exclusive

Donor-funded research looks at new targets for vaccination

In the more than 160,000 years that modern man has walked the earth, the human immune system has probably been the body's "most valuable player" among factors that have kept our species afloat. That's why cancer researchers are focusing more attention on ways of tapping the body's natural ability to fend off disease

This field, called immunotherapy, or biological therapy, shows great potential for becoming a fourth arm of cancer treatment - along with surgery, radiation therapy and chemotherapy - on the short list of effective anti-cancer strategies.

Kelvin Lee, MD, Chair of Roswell Park's Department of Immunology, believes that immunotherapy must become an integral part of standard therapy early in the course of treatment. "Right now we look at immunotherapy when a patient has run out of all other options," he explains, "and it's probably not going to work very well in that setting. We need to look at it more comprehensively. Can we vaccinate patients who have pre-malignant or very early cancer, when they still have an immune response against cancer? Can we try to boost the immune system when it's failing, but still there?"

Molecule shows "very high potential" for preventing breast cancer

Early involvement of the immune system is central to the work of Ashwani Sood, PhD, Assistant Member in Immunology. Sood and his research team have identified a molecule called Prostate-Derived Ets Factor (PDEF), which is found in high volumes in breast tumors, but at very low levels in normal tissue. That characteristic gives it great potential as a "target" for a vaccine that would trigger the immune system to attack the tumor while sparing normal cells.

Sood says PDEF may prove as important as HER-2, a protein that controls cell growth and that can cause a particularly aggressive form of breast cancer when it's over-produced. Studies of HER-2 led to the development of the drug Herceptin (trastuzumab), which attaches itself to - and inhibits the growth of - breast cancer cells with high HER-2 levels. The introduction of Herceptin has extended the lives of many women with HER-2-positive breast cancer, and Sood notes that high volumes of PDEF are found in "almost twice as many tumors as HER-2, so a PDEF vaccine could have even greater impact."

Because PDEF is also found in ovarian and prostate tumors, the research could have implications for creating vaccines against those cancers as well.

Research models have demonstrated that PDEF works in the same way as HER-2. With a competitively-awarded scientific advisory grant from the Roswell Park Alliance Foundation (an allocation of donor dollars), Sood and his team have proved that vaccination with PDEF "does induce an immune response, and can delay tumor development," he says.

In the face of drastic cuts in federal funding for cancer research, Alliance support has kept Sood and his colleagues moving forward with this promising investigation. "PDEF is such an important molecule," he says. "We need to take it further."

"The data we have almost ready for a clinical trial. All we need to demonstrate is that PDEF is immunogenic and can induce immunity in breast cancer patients."

Adds Lee, "With the investment the Institute has made in the Department of Immunology, we are well positioned to offer cutting-edge therapies to patients who have cancer. That’s the strength of an institution like Roswell Park."