Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Am J Transplant ; 17(4): 931-943, 2017 04.
Article in English | MEDLINE | ID: mdl-28027623

ABSTRACT

Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation.


Subject(s)
Graft Rejection/prevention & control , HLA-A2 Antigen/immunology , Receptors, Antigen/immunology , Skin Transplantation/adverse effects , T-Lymphocytes, Regulatory/immunology , Allografts , Animals , Graft Rejection/etiology , Graft Survival/immunology , Heterografts , Humans , Leukocytes, Mononuclear , Mice , Mice, Inbred BALB C , Transplantation Tolerance/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...