Prospective clinical testing of regulatory dendritic cells (DCreg) in organ transplantation

Frontiers in Immunology

ALAN F ZAHORCHAK¹  ANGUS W THOMSON¹  Diana M Metes¹  Fadi G. Lakkis¹  Mohamed B. Ezzelarab¹  Lisa H. Butterfield¹ 

[1] UNIVERSITY OF PITTSBURGH;

关键词: Dendritic Cells;    cell therapy;    Immune Regulation;    Renal transplantation;    immune monitoring;   

DOI  :  10.3389/fimmu.2016.00015

来源: DOAJ

【 摘 要 】

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

【 授权许可】

Unknown