Unmasking the Cancer Rogues
Some cancer cells play a game of cat and mouse with the body’s immune system.
They can hide because they don’t carry proteins on their surface that immune system cells need to identify them as diseased. As a result, these undetected cancer cells fail to trigger the immune system and proliferate.
Haval Shirwan wants to unmask the rogue cancer cells so that the immune system can find and destroy them.
Shirwan is an associate professor in the department of microbiology and immunology in U of L’s School of Medicine. He also is a University Scholar and director of the Molecular Immunology Program in the Institute for Cellular Therapeutics.
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U of L immunologist Haval Shirwan believes his method of helping the immune system see and destroy hidden cancer cells could be an improvement on traditional gene therapy, which is time-consuming and often has dangerous side effects. Photo © Courier-Journal
He has developed a treatment that so far has killed tumors in mice and in human cells in the lab. It shows promise for patients once human trials begin, possibly as early as this fall.
“This is a very innovative technique,” Shirwan says. “The innovation is that we can directly put proteins on the surface of tumor cells instead of using traditional gene therapy, which is not always reliable.”
Shirwan’s technique combines human protein parts with a genetically engineered protein. The resulting substance attaches itself to the cancer cells. The immune system can then “see” the disease cells and begin fighting both treated and untreated cancer cells. Shirwan also developed a substance that coats the cancer cells and helps the re-engineered proteins bind to them.
Three patents are pending on parts of the technique.
With entrepreneur Bill Pearse, Shirwan co-founded ApoImmune Inc., a company that will bring the discovery to market and develop other products that could utilize the body’s immune system to fight disease. Shirwan is ApoImmune’s chief scientific officer, Pearse is its vice president of operations and Steven T. Downey is its chief executive officer.
Raising funds to begin the human trials has been a challenge in the tight venture capital market of recent years, Shirwan says.
“It is expensive to conduct the tests, such as for toxicity, required by the Food and Drug Administration before you can begin human trials,” he adds.
The research so far has been supported by the National Institutes of Health, which has provided millions for the studies and for small business development. Jewish Hospital HealthCare Services also has granted research funds to ApoImmune.
Shirwan says his technique has advantages over traditional immunotherapy such as gene therapy.
In the latter, human DNA is altered to boost immune response but the process sometimes can be dangerous and time-consuming.
Shirwan says his approach more directly engages the immune system.
“It’s safe because we’re only working with proteins and delivering an extremely effective activation signal,” he says. “We have greater control over the process and it’s fast; it only takes a couple of hours. The immune system stimulation is much improved.”
Growing Their Own
Proteins used in medicine can be grown inside plants, insects or other animals.
Shirwan is using fruit flies as a growing medium because, he says, they produce proteins in ways similar to humans, they don’t carry any animal or human viruses and they can produce large quantities of protein. Using existing recombinant DNA techniques, ApoImmune’s proprietary gene is introduced into the genome of an insect’s cells. The resulting protein is secreted into a tissue culture and purified.
Another potential growing medium for the protein is in tobacco plants.
That would be ironic because one of the first human trials for the ApoImmune protein product would be in lung cancer patients, Shirwan says. ApoImmune is in talks with Large Scale Biology Corp., a California biotech firm to pursue that method of growing proteins.
Colon cancer patients also would be among the first to receive the therapy. Jewish Hospital in Louisville is slated as the site for the trials.
Shirwan was recruited to U of L in 1999 as part of the state’s “Bucks for Brains” program that helps bring top researchers to Kentucky universities. He conducted research into his technique at the National Institute of Transplantation and elsewhere before coming to U of L.
ApoImmune’s labs are in the MedCenter Two biomedical business incubator complex operated by the Louisville Medical Center Development Corp.
Shirwan and colleagues caution that widespread application of the new technique could be a decade away.
Meanwhile, word of Shirwan’s discoveries is getting out to the scientific community.
“We’ve been accepted for the first time for a poster presentation at the American Society for Clinical Oncology,” Shirwan says.
The University of Louisville Research Foundation and Shirwan hold a financial interest in ApoImmune. Multiple steps to ensure patient protection and research integrity have been taken consistent with the university’s policy for oversight of institutional financial interests in research.
