Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates

A. M. Freitas, K. P. Samy, A. B. Farris, F. V. Leopardi, M. Song, L. Stempora, E. A. Strobert, J. A. Jenkins, A. D. Kirk, L. C. Cendales*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 CD2hi 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.

Original languageEnglish
Pages (from-to)2240-2249
Number of pages10
JournalAmerican Journal of Transplantation
Volume15
Issue number8
DOIs
StatePublished - 1 Aug 2015
Externally publishedYes

Keywords

  • animal models: nonhuman primate
  • calcineurin inhibitor (CNI)
  • costimulation
  • fusion proteins and monoclonal antibodies: belatacept
  • immunosuppressant
  • reconstructive transplantation
  • rejection
  • translational research/science
  • vascularized composite

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