Researchers at the University of Connecticut
have found a new way to identify protein mutations in cancer cells. The novel
method is being used to develop personalized vaccines to treat patients with
ovarian cancer.
"This has the potential to dramatically change how we treat
cancer," says Dr. Pramod Srivastava, director of the Carole and Ray Neag
Comprehensive Cancer Center at UConn Health and one of the principal investigators
on the study. "This research will serve as the basis for the first ever
genomics-driven personalized medicine clinical trial in immunotherapy of
ovarian cancer, and will begin at UConn Health this fall," Srivastava
says.
The researchers focused their clinical trial on patients with
ovarian cancer because the disease usually responds well to surgery and
chemotherapy in the short term, but often returns lethally within a year or
two. That gives researchers the perfect window to prepare and administer the
new therapeutic vaccines, and also means they may be able to tell within two
years or so whether the vaccine made a difference. If the personalized vaccines
prove to be safe and feasible, they'll design a Phase II trial to test its
clinical effectiveness by determining whether they prolong patients' lives.
Identifying tiny differences
In order for the immune system to attack cancers, it first has
to recognize them. Every cell in the body has a sequence of proteins on its
exterior that acts like an ID card or secret handshake, confirming that it's
one of the good guys. These protein sequences, called epitopes, are what the
immune system 'sees' when it looks at a cell. Cancerous cells have epitopes,
too. Since cancer cells originate from the body itself, their epitopes are very
similar to those of healthy cells, and the immune system doesn't recognize them
as bad actors that must be destroyed. But just as even the best spy
occasionally slips up on the details, cancer cell epitopes have tiny
differences or mistakes that could give them away, if only the immune system
knew what to look for.
"We want to break the immune system's ignorance,"
Srivastava says. For example, there could be 1,000 subtle changes in the cancer
cell epitopes, but only 10 are "real," meaning significant to the
immune system. To find the real, important differences, Mandoiu, the
bioinformatics engineer, took DNA sequences from skin tumors in mice and
compared them with DNA from the mice's healthy tissue.
Previous researchers had done this but looked at how strongly
the immune system cells bound to the cancer's epitopes. This works when making
vaccines against viruses, but not for cancers. Instead, Srivastava's team came
up with a novel measure: they looked at how different the cancer epitopes were
from the mice's normal epitopes. And it worked. When mice were inoculated with
vaccines made of the cancer epitopes differing the most from normal tissue,
they were very resistant to skin cancer.
Theoretically, this approach could work for other cancers,
although the research has yet to be done.
Creating a safe, effective cancer vaccine is one of the major
long-term goals of personalized medicine. Using a different approach than the
one described in this paper, Srivastava's research has already created a
vaccine against kidney cancer, which is in clinical use and commercially
available in Russia.
"It is known that patients have genetic sequences that make
them better candidates for some drugs than others. And we can figure that out
much more easily now than five years ago," Srivastava says. The novelty of
Srivastava's approach in this new research is that it results in a drug
specifically designed for a single person. If the approach proves safe and
effective, it would be the ultimate in individualized medicine.
Posted By:-
Bioinformatice Department
No comments:
Post a Comment