Vaccine and Biotherapeutic Linked in New Effort to Combat Cancer
저자: 업로드:2015-07-21 조회수:
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."
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