Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates.

Journal Article (Journal Article)

Vascularized composite allografts (VCAs) are technically feasible. Similar to other organ transplants, VCAs are hampered by the toxicity and incomplete efficacy associated with conventional immunosuppression. Complications attributable to calcineurin inhibitors remain prevalent in the clinical cases reported to date, and these loom particularly large given the nonlifesaving nature of VCAs. Additionally, acute rejection remains almost ubiquitous, albeit controllable with current agents. Costimulation blockade offers the potential to provide prophylaxis from rejection without the adverse consequences of calcineurin-based regimens. In this study, we used a nonhuman-primate model of VCA in conjunction with immunosuppressive regimens containing combinations of B7-specific costimulation blockade with and without adhesion blockade with LFA3-Ig to determine what adjunctive role these agents could play in VCA transplantation when combined with more conventional agents. Compared to tacrolimus, the addition of belatacept improved rejection free allograft survival. The combination with LFA3-Ig reduced CD2(hi) memory T cells, however did not provide additional protection against allograft rejection and hindered protective immunity. Histology paralleled clinical histopathology and Banff grading. These data provide the basis for the study of costimulation blockade in VCA in a relevant preclinical model.

Full Text

Duke Authors

Cited Authors

  • Freitas, AM; Samy, KP; Farris, AB; Leopardi, FV; Song, M; Stempora, L; Strobert, EA; Jenkins, JA; Kirk, AD; Cendales, LC

Published Date

  • August 2015

Published In

Volume / Issue

  • 15 / 8

Start / End Page

  • 2240 - 2249

PubMed ID

  • 26139552

Pubmed Central ID

  • PMC4918096

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

Digital Object Identifier (DOI)

  • 10.1111/ajt.13379


  • eng

Conference Location

  • United States