Abstract | Investigators | Background | Resources

When kidneys are transplanted between genetically nonidentical individuals, they are invariably destroyed by the immune system by a process known as rejection. Currently, immunosuppressive drugs effectively prevent rejection but must be continued indefinitely and are complicated by drug side effects, infection, and cancer. The goal of this research is to test a new strategy involving recently developed drugs (Campath-1H, a monoclonal antibody binding to lymphocytes and monocytes; and Prograf and rapamycin, drugs affecting T lymphocytes) to determine whether this combination enables patients to discontinue long-term immunosuppressive therapy in the absence of rejection.

A laboratory test - trans-vivo DTH assay - has been developed that may tell us whether or not a patient is at risk for rejection. This test has not yet been clinically validated in terms of predicting successful withdrawal of immunosuppressive drugs, but is in the process of such testing. We propose to use this test in parallel with protocol kidney transplant biopsies to make predictions on whether patients in this clinical trial can be successfully withdrawn from rapamycin. Evidence from a pilot study at the University of Wisconsin suggests that even if study participants develop rejection, it can be successfully reversed. In these cases, the kidney transplant can be salvaged and the patient returned to an immunosuppressive drug regimen. Therefore, we do not anticipate that a rejection episode will result in graft loss since careful monitoring and rescue therapy would be used.

The Campath-1H antibody is given to the patients on the day of their kidney transplant and on days 1, 3, 5, and 14. Patients would also receive 60 days of Prograf therapy but come off this drug at 60 days if they remain rejection-free. During the first year of the clinical trial, all patients will receive daily rapamycin therapy. One year post-transplant, if protocol biopsies are free of acute or chronic rejection, rapamycin will be discontinued. Successful discontinuation of rapamycin therapy with maintained kidney transplant function would satisfy the goal of immunologic tolerance, which is the overall goal of the ITN. This pilot study in 10 patients will focus on well-matched primary kidney transplants (0-3 HLA mismatches). This plan is based in human and animal models of organ transplantation that 1) the degree of MHC mismatch correlates with the likelihood of rejection and tolerance and 2) transplant tolerance requires time to develop an appropriate immunologic environment including the absence of rejection.

Participating Investigators

	Stuart Knechtle, University of Wisconsin Medical School, Madison, WI
	William Burlingham, University of Wisconsin Medical School, Madison, WI
	Hans Sollinger, University of Wisconsin Medical School, Madison, WI
	Lee Brettman, Millennium Pharmaceuticals, Cambridge, MA

Background Articles

	Campath 1H allows Low dose cyclosporine monotherapy in renal transplantation - Transplantation [go]
	Human allograft acceptance is associated with immune regulation - J Clin Invest [go]
	Primate renal transplants using immunotoxin - Surgery [go]

Resources & Interesting Links

From laboratory to clinic: the story of CAMPATH-1 - Meth Mol Med [go]