Loyola researchers try to bolster fight against infection, cancer

Human tests of immune-boosting technique about 3 years away

By Steven Ross Johnson, Special to the Tribune

March 21, 2012


Researchers at Loyola University Medical Center have recently made a discovery that could be the first significant step toward helping the body's immune system put up a more effective fight against severe infections and possibly cancer.

In a study published in the February edition of the Nature Medicine journal, the Loyola researchers reported developing a technique that they say delivers DNA to the immune system, instructing cells to overproduce proteins that help develop stronger T cells — a type of white blood cell instrumental for the body's defense against illness.

Among the various types of T cells, CD8, or "killer" T cells, are responsible for attacking pathogens, while antigen-presenting, or "instructor" T cells, program CD8 T cells to attack. In order for the killer T cells to become truly effective, they also require the aid of what's known as CD4, or "helper" T cells. In HIV and cancer patients, the killer T cells are suppressed because CD4 T cells are compromised, or destroyed altogether.

"When a CD8 is activated in the absence of CD4s, or with compromised CD4s, they're not only deficient in killing, but they also die. They don't survive, so you have no memory," said the study's senior author, Dr. Jose A. Guevara-Patino, an associate professor of oncology at Loyola's Stritch School of Medicine. "That's the key of all immunity. ... Every time you encounter the pathogen, you can mount a fast defense to protect the body."

The process developed by the research team involves delivering DNA by a device known as a gene gun into instructor cells, which then unlocks the killer properties of the CD8 T cells, allowing them to still fight infections and tumors even if the helper T cells are compromised.

The idea for the technique, Guevara-Patino said, came after observing the way in which killer T cells behaved within autoimmune disorders, such as celiac disease, a genetic disorder where exposure to a protein found in gluten causes a reaction in the immune system that damages the gastrointestinal tract.

"If I could harness the power of that receptor to guide the killer cells against pathogens or cancer, maybe we have a shot," Guevara-Patino said.

The technique was first tested in mice with low counts of CD4 T cells, and then studied by examining the CD8 T cells from HIV patients with low counts of CD4s, Guevara-Patino said.

"What we saw was we were able to reproduce the same effects (as seen in mice)," Guevara-Patino said. "We were able to rescue T cells that were otherwise helpless from HIV patients."

Guevara said the possibilities for the technique could possibly lead one day to the development of effective vaccines for a wide array of diseases, including HIV and cancer.

"When you now provide this alternative help, which is like jet fuel for the CD8s, now the CD8s are responding to things they otherwise wouldn't," Guevara-Patino said. "Part of the beauty of this approach is that it can be incorporated into multiple platforms of immunotherapy, whether it's for chronic infectious diseases or cancer."

Clinical trials of the study within cancer patients are expected to begin in about three years, where questions regarding the kind of effect the technique will have on a living human body can be fully examined, Guevara-Patino said.

"It's definitely a step forward in trying to characterize what's there and how these interactions are supposed to occur," said Dr. Neil Kao, an internal medicine specialist at the Allergic Disease and Asthma Center in Greenville, S.C. "First you have to understand how things work. However, it is a whole another gigantic step as far as identifying something else that will interfere with how things work along with not causing side effects."

The study was conducted over a five-year period, and received major funding from the American Cancer Society and the National Institutes of Health.