Gene Transfer of the S24F Regulated on Activation Normal T-Cell Expressed and Secreted–Chemokine Ligand 5 Variant Attenuates Cardiac Allograft Rejection

Abstract

S24F is an important component of the chemokine network involved in regulating the biologic activity of RANTES, and its expression can be used in the prevention and treatment of cardiac allograft rejection.

CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a Mycophenolate-based Immunosuppressive Regimen

“…Studies that have demonstrated incremental benefits in terms of preventing or slowing the progression of CAV have been conducted on rodent models. 24-27 This pilot study evaluated the efficacy of a CXCR4 antagonist combined with CNI-free ISDs for controlling both acute rejection and CAV in a swine model of allogeneic heterotopic cardiac transplantation. A favorable survival trend was observed in the burixafor 2D group, and a significantly prolonged graft survival was achieved through intensified treatment in the burixafor 2D + B group.…”

Virus-Derived Chemokine Modulating Protein Pre-Treatment Blocks Chemokine–Glycosaminoglycan Interactions and Significantly Reduces Transplant Immune Damage

“…Grafts were assessed for histological analysis with routine hematoxylin and eosin (H&E) staining as well as immunohistochemical (IHC) staining. Total inflammatory cell infiltrate area and scar (fibrotic) areas were measured and normalized to the total renal allograft implant area [ 7 , 8 , 9 , 12 , 13 , 35 , 38 ]. The diameter of the inflammation and scar were similarly measured and normalized to total graft diameter.…”

“…M-T7 is a 37 KDa myxoma virus-derived purified protein that binds C, CC and CXC classes of chemokines, blocking chemokine to GAG binding [ 7 , 8 , 9 , 10 , 11 ]. In prior studies, modifying chemokine and chemokine receptor activity reduced transplant damage and rejection [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Treatment after transplant with M-T7 reduced the aortic allograft vascular inflammation at 30 days follow-up [ 8 ].…”

“…Modifying the endothelial polysaccharides and GAG composition also reduced immune cell response and organ damage in a separate series of transplant models, including aortic and renal allograft studies. [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

“…Treatment of grafts prior to surgical transplant is postulated to improve graft outcomes by decreasing inflammation and organ damage before transplantation [ 10 , 11 , 12 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Dopamine pre-treatment of donor organs has demonstrated reduced renal allograft rejection and superior long-term graft survival [ 24 ].…”