Vaccine and Biotherapeutic Linked in New Effort to Combat Cancer

A new study at the University of Wisconsin-Madison has linked two seemingly unrelated cancer treatments that are both now being tested in clinical trials. One therapy is a vaccine that targets a structure on the outside of cancer cells, while the other is an altered enzyme that breaks apart RNA and causes the cell to commit suicide. The study (“Human Cancer Antigen Globo H Is a Cell-Surface Ligand for Human Ribonuclease 1”) appears in ACS Central Science.

The new understanding could help both approaches, says UW-Madison professor of biochemistry Ronald Raines, Ph.D., who has long studied ribonucleases. In 1998, he discovered how to alter one ribonuclease to avoid its deactivation in the body. Soon thereafter, he found that the engineered ribonuclease was more toxic to cancer cells than to others.

The current study began as an effort to figure out why the ribonuclease was selective for cancer cells. To identify which structure on the cell surface helped it enter the cell, Dr. Raines screened 264 structures using a specially designed chip. The winner was a carbohydrate called Globo H.

“We were surprised and delighted to see that because we already knew that Globo H is an antigen that is abundant in many tumors,” says Dr. Raines. “Globo H is under development as the basis for a vaccine that will teach the immune system to recognize and kill cancer cells.”

Dr. Raines patented the advance through the Wisconsin Alumni Research Foundation and co-founded Quintessence Biosciences in Madison. The company licensed the patent from WARF and began early-phase human trials with the ribonuclease at the UW Carbone Cancer Center and MD Anderson Cancer Center.

Working with Samuel Danishefsky, Ph.D., who solved the difficult problem of synthesizing Globo H at the Memorial Sloan-Kettering Cancer Center, Dr. Raines found that reducing the Globo H display on the surface made breast cancer cells less vulnerable to ribonucleases like those that Quintessence is testing. “This was exciting, as we now have a much clearer idea of how our drug candidate is working,” notes Dr. Raines.

The picture that emerges from the research is of ribonucleases patrolling our bodies, looking for telltales of cancer cells, explains Dr. Raines, adding that “We are working to demonstrate this surveillance more clearly in mice, but don’t have direct evidence yet.”

As other scientists test whether using a vaccine will start an immune attack on Globo H, Dr. Raines points out that, “we are probing a different type of immunity. This innate immunity does not involve the immune system. It’s a way for our bodies to fight cancer without using white blood cells or antibodies, just an enzyme and a carbohydrate.”