PURPOSE OF REVIEW: We discuss the use of tolerogenic dendritic cells (TolDCs) as a therapeutic tool in solid organ transplantation, with particular emphasis on recent experimental and preclinical data supporting the clinical translation of TolDC therapy. RECENT FINDINGS: TolDC have been successfully used in rodents to promote long-term allograft survival. Although most studies have focused on donor dendritic cells or donor antigen-pulsed dendritic cells, our group investigated a strategy based on the administration of autologous dendritic cells (not pulsed with donor antigens). We discuss the therapeutic efficacy, mechanisms, and potential risks and advantages of each strategy. We also highlight recent findings on the generation of clinical grade human TolDC from blood monocytes. Finally, we discuss preliminary experience with dendritic cells in humans and critical issues regarding the implementation of TolDC therapy to clinical organ transplantation. SUMMARY: TolDC hold therapeutic promise for the treatment of transplanted patients. Cell therapy with unpulsed, autologous dendritic cells appears as a well tolerated, clinically relevant approach that might help in improving long-term allograft survival and limit the harmful effects of immunosuppressive treatments.
PURPOSE OF REVIEW: We discuss the use of tolerogenic dendritic cells (TolDCs) as a therapeutic tool in solid organ transplantation, with particular emphasis on recent experimental and preclinical data supporting the clinical translation of TolDC therapy. RECENT FINDINGS: TolDC have been successfully used in rodents to promote long-term allograft survival. Although most studies have focused on donor dendritic cells or donor antigen-pulsed dendritic cells, our group investigated a strategy based on the administration of autologous dendritic cells (not pulsed with donor antigens). We discuss the therapeutic efficacy, mechanisms, and potential risks and advantages of each strategy. We also highlight recent findings on the generation of clinical grade human TolDC from blood monocytes. Finally, we discuss preliminary experience with dendritic cells in humans and critical issues regarding the implementation of TolDC therapy to clinical organ transplantation. SUMMARY: TolDC hold therapeutic promise for the treatment of transplanted patients. Cell therapy with unpulsed, autologous dendritic cells appears as a well tolerated, clinically relevant approach that might help in improving long-term allograft survival and limit the harmful effects of immunosuppressive treatments.
Authors: Mohamed B Ezzelarab; Lien Lu; Hao Guo; Alan F Zahorchak; William F Shufesky; David K C Cooper; Adrian E Morelli; Angus W Thomson Journal: Transplantation Date: 2016-01 Impact factor: 4.939
Authors: M B Ezzelarab; D Raich-Regue; L Lu; A F Zahorchak; A Perez-Gutierrez; A Humar; M Wijkstrom; M Minervini; R W Wiseman; D K C Cooper; A E Morelli; A W Thomson Journal: Am J Transplant Date: 2017-02-02 Impact factor: 8.086
Authors: Christian Andreas Radu; Sebastian Fischer; Yannick Diehm; Otto Hetzel; Florian Neubrech; Laura Dittmar; Christian Kleist; Martha Maria Gebhard; Peter Terness; Ulrich Kneser; Jurij Kiefer Journal: Langenbecks Arch Surg Date: 2017-08-19 Impact factor: 3.445
Authors: M Segovia; C Louvet; P Charnet; A Savina; G Tilly; L Gautreau; L Carretero-Iglesia; G Beriou; I Cebrian; T Cens; L Hepburn; E Chiffoleau; R A Floto; I Anegon; S Amigorena; M Hill; M C Cuturi Journal: Am J Transplant Date: 2014-04-14 Impact factor: 8.086