PATIENTS undergoing organ transplants at a hospital in the US have begun a
pioneering course of treatment aimed at preventing rejection of their new
organs. By reprogramming the patients鈥� immune systems before they receive the
organs, the surgeons hope to trick the patients鈥� bodies into accepting the new
organs as 鈥渟elf鈥�.
If the reprogramming works, donor organs would not even need to match
transplant patients鈥� tissue. The system, pioneered by David Sachs of the
Massachusetts General Hospital (MGH) in Boston, could also mean people with new
organs will be able to survive without the drugs that prevent their immune
systems from attacking the transplant
Surgeons led by Benedict Cosimi at the MGH are testing Sachs鈥檚 three-stage
treatment regime on patients. The 鈥淎lloMune鈥� regime, which is now being
developed by BioTransplant, a company based at Charlestown, Massachusetts, has
already been tested successfully in primates in previous trials.
Advertisement
Patients will first receive a rat antibody codenamed BTI-322. This antibody,
discovered by researchers at the Catholic University of Leuven in Belgium,
neutralises mature T cells, the sentinels of the body鈥檚 immune system.
鈥淭hese T cells form the body鈥檚 front line of defence against foreign material
entering the body,鈥� says Elliot Lebowitz, the president of BioTransplant.
Normally, they would register a transplanted organ as foreign and orchestrate
its destruction.
In experiments on primates, doses of antibody over 10 days inactivated all
mature T cells in the animals鈥� bloodstreams. When patients have undergone
similar 鈥減urges鈥�, they will receive radiation treatment to create a space in
their bone marrow where surgeons will transplant bone marrow from the organ
donor. This transplanted tissue creates a 鈥渃himeric鈥� bone marrow containing
cells from both patient and donor. This is the key to reprogramming the patient鈥�
immune system. The process takes place in the thymus, the gland where T cells
are primed to attack 鈥渇oreign鈥� material, or taught not to attack native
tissue.
Cells from the chimeric bone marrow arrive at the thymus as they begin to
evolve into T cells. In the thymus, this new set of T cells is 鈥渢aught鈥� to
accept tissue from both the host and donor as 鈥渟elf鈥�. 鈥淭he original immune
system is inactivated and a new one created in its place,鈥� says Lebowitz.
Finally, patients will receive the organ itself. The researchers hope that
the new immune system will always accept the organ as self. As a precaution,
patients will receive the usual immunosuppressive drugs for a month or so to
prevent rejection. Experiments at MGH have shown that the original arsenal of T
cells reappears in the new immune system, minus cells that would have attacked
the donor tissue. Likewise, the new immune system is primed to destroy anything
that threatens the newly implanted tissue.
Lebowitz says that details of the experiments are being kept secret to
protect the identity of the patients. But he expects the first results to be
made public some time next year. 鈥淚f it works, it鈥檚 a really big deal,鈥� he says.
Not only are immunosuppressive drugs expensive, they can leave patients
vulnerable to infection.
