Researchers are working on a new approach to improving xenotransplantation tolerance: the genetic engineering of bone marrow.
In the September 18 issue of Science (1998;281:1845-1847), Jennifer L. Bracy, David H. Sachs, and John Iacomini of Massachusetts General Hospital explained that humans and apes make antibodies to alpha-Gal, a carbohydrate that is present in other mammals. However, if pig organs are transplanted into humans, the alpha-Gal carried in the pig organs could signal the human antibodies to attack the porcine tissue. The researchers "theorized that putting the gene that produces alpha-Gal into a transplant recipients' bone marrow ... could help. If the alpha-Gal was already there, newly forming antibodies wouldn't know to attack it elsewhere in the body," the Associated Press explained.
The investigators created mice whose ability to fight alpha-Gal mimicked that of humans. Once the bone marrow of the mice was genetically altered, the mice stopped producing antibodies to alpha-Gal.
The findings indicate "that we have specifically re-educated the recipient animal's immune system, potentially allowing the acceptance of a porcine antigen as its own," said Dr. Iacomini.
A press release issued by BioTransplant, Inc., of Charlestown, Mass., with whom the investigators are collaborating, said that the study represents "the first demonstration that preexisting natural antibodies can be inhibited using a gene therapy approach without any additional immunosuppression therapy."
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