特集「移植免疫の最前線」
混合キメラによる免疫寛容誘導の臨床応用
キーワード:
allograft tolerance,
chimerism,
hematopoietic stem cell transplantation,
donor bone marrow transplantation,
kidney transplantation
2017 年 52 巻 6 号 p. 495-503
詳細
2017 年 52 巻 6 号 p. 495-503
Induction of hematopoietic chimerism is thus far the only approach that was proven to be effective to induce allograft tolerance in nonhuman primates (NHP) and humans. In the United States, three centers have reported clinical trials for tolerance induction in recipients of living donor kidney transplants via donor hematopoietic stem cell transplantation. In these clinical trials, successful renal allograft tolerance induction has been achieved following induction of either transient mixed or persistent full donor chimerism. At Massachusetts General Hospital, based upon observations in murine models, we developed nonmyeloablative regimens to induce allograft tolerance through the mixed chimerism approach in NHP and humans. Despite detectable chimerism induced by our nonmyeloablative conditioning regimen typically disappears within 30-60 days, renal allograft tolerance was reproducibly achieved in MHC-mismatched kidney transplant recipients.
Improving the consistency of tolerance with less morbidity and extending the approach to deceased donor transplantation are critical next steps for wider clinical applications.
