Why does the review article highlight the concept of chimerism?
Dr. Ildstad: Chimerism refers to the coexistence of more than one genetically disparate component in one recipient. The most common chimeras are those mythological figures on temples and cathedrals worldwide. The chimerism we use is bone marrow chimerism (the donor hematopoietic stem cell coexists peacefully in the recipient).
How soon might we see a drastic reduction in the need for post-transplant immunosuppression?
Dr. Ildstad: We are currently experiencing tolerance and successful elimination of immunosuppression for kidney transplants in the clinic with approximately 86% success.
Today, kidney-transplant recipients can expect to be on lifelong immunosuppressive therapy. How do you see this scenario changing?
Dr. Ildstad: Hopefully, we can avoid immunosuppression completely after one year post-transplant and avoid all of the associated toxicities.
Are there any concerns regarding or disadvantages to the achievement of donor-specific tolerance and the elimination of post-transplant immunosuppressive therapy?
Dr. Ildstad: No.
What changes would be needed in the renal-transplant process for donor-specific tolerance to be achieved?
Dr. Ildstad: The subject would undergo conditioning to make space for the donor bone marrow. This has been managed to date as an outpatient procedure. The donor is treated with GCSF to expand facilitating cells and stem cells and cause their egress into the peripheral blood, and the mobilized hematopoietic product is collected by apheresis.
How prominent a role does kidney transplantation have in donor-specific tolerance research?
Dr. Ildstad: The advantage of kidney transplantation for a phase I study is that living-donor kidney transplants are electively scheduled and do not rely upon the unpredictable availability of deceased donors.
What is the next step needed to advance the goal toward donor-specific tolerance?
Dr. Ildstad: More advanced clinical trials are being planned to confirm our early results. Ultimately, pivotal clinical trials will be performed and eventually submitted to FDA and other health authorities.