The team also will explore the more localized approach used by fetuses and tumors, where specific tissue puts up a sort of immune barrier by expressing IDO. They'll use a powerful viral vector as a vehicle to deliver the IDO gene directly into the tissue to be transplanted, turning the cells into "IDO over-expressers," Dr. Mellor said.
The vector was developed with the help of Georgia Research Alliance funding and Dr. Yukai He, a member of the MCG Cancer Center's Immunotherapy Program and GRA Distinguished Investigator who specializes in cancer vaccine development.
"We have to try both directions: putting the IDO gene in locally or giving it systemically. We know the mechanism works in principle: that IDO is a good way to protect transplants. But we don't know what is the most effective way," Dr. Mellor said.
Mason Trust funds also will enable expansion of studies in human samples by Dr. Anatolij Horuzsko, an immunologist in the MCG Center for Molecular Chaperone/Radiobiology and Cancer Virology, and Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the School of Medicine.
Several forms of HLA-G are effective at inhibiting the immune response similar to the way fetuses and tumors use IDO but Dr. Horuzsko has shown the dimer version comprised of two chemically attracted monomers or molecules is the best HLA-G at blocking transplant rejection in a mouse with a skin graft.
He already has measured HLA-G dimer levels in the blood of more than 50 kidney transplant patients and found pretty much what he's seen in his animal studies: those who don't reject their new kidneys have higher levels o
|Contact: Toni Baker|
Medical College of Georgia