UAMS Research with Tobacco-funded Machines

By todd

The State of Arkansas dedicated its revenue from the 1998 settlement to research, prevention, and treatment for smoking-related illnesses, with some of the funds going to the Arkansas Biosciences Institute, a consortium of research institutions. ABI allotted $365,000 to UAMS for two optical biosensors manufactured by Biacore Inc. Biacore is a world leader in detection and monitoring of biomolecular binding using surface plasmon resonance (SPR) technology.

Thomas Kieber-Emmons, Ph.D., is using the two machines in his research on possible vaccines that will give cancer patients better immunity against recurrence of the disease. The Biacore units are the first in Arkansas. Scientists at UAMS will be able to use them in research on other diseases, too.

By monitoring the progress of biomolecular interactions in real time, Biacore systems can provide answers to a series of basic questions about biomolecules and their interactions. That technology has ramifications for a wide range of cancer research, but is especially important to the work of Kieber-Emmons, who was recently recruited from the University of Pennsylvania to UAMS as director of basic breast cancer research at the ACRC, is a professor of pathology in the UAMS College of Medicine, and holds the Josetta Edwards Wilkins Chair in Breast Cancer Research in the college.

Kieber-Emmons, an immunologist, is experimenting with ways to affect a cellular response, previously thought to only be possible in reaction to protein antigens, to carbohydrate antigens that are found on cancer cells.

Antibodies can confront carbohydrate antigens in the classic immune response to rid the body of bacteria, viruses, and some tumor cells. But antibody immunity is not as effective against tumor cells as cellular immunity, in which T cells are activated to recognize pieces of tumor antigen in order to destroy the tumor. Carbohydrates are processed by the immune system differently than protein antigens, and therefore are not typically recognized by the T cells.

“So what we’ve been doing is figuring out the molecular structure of carbohydrates and then recreating them through computer generation into an amino acid compound called a peptide,” Kieber-Emmons said of his unique research. “In essence it’s a protein antigen that mimics a carbohydrate antigen. These mimics are also called mimotopes. Using mimicry, we can trick the immune system into targeting antigens that are otherwise difficult to target, providing, in principle, long-lasting immunity.”

Since T cells once activated carry an immuno “memory” for the peptide, but do not for the carbohydrate, the ability to convert carbohydrate antigen to peptide means the body can stand guard against that tumor for years to come. So vaccines can be developed that were never thought possible to prevent reoccurrence of tumors.

Additionally, carbohydrate antigens are much more universal than protein antigens, meaning carbohydrate-mimicking peptide vaccines could treat any number of diseases. “With these mimotopes, we’re able to elicit an antibody response and a cellular response simultaneously,” Kieber-Emmons said. “The types of carbohydrates we’re looking at are found in a variety of different cancer types. We have studies on melanoma; we have studies in breast cancer; we have studies in ovarian, prostate, pancreatic cancers. These antigens are also found on pathogens like HIV for which we are also developing mimotopes.”

The new Biacore units allow Kieber-Emmons to isolate the best possible binding of carbohydrate antigen to antibody and then copy those molecular structures through computer modeling. The resulting peptide mimics allow scientists to track down cancer cells that previously could not be affected through immuno therapy. “We needed this type of instrumentation, and in time other people at UAMS will extend their research to utilize Biacore,” he said.