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

Publication ,  Journal Article
Freitas, AM; Samy, KP; Farris, AB; Leopardi, FV; Song, M; Stempora, L; Strobert, EA; Jenkins, JA; Kirk, AD; Cendales, LC
Published in: Am J Transplant
August 2015

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.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

August 2015

Volume

15

Issue

8

Start / End Page

2240 / 2249

Location

United States

Related Subject Headings

  • Surgery
  • Primates
  • Neovascularization, Pathologic
  • Animals
  • Allografts
  • 3204 Immunology
  • 3202 Clinical sciences
  • 11 Medical and Health Sciences
 

Citation

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ICMJE
MLA
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Freitas, A. M., Samy, K. P., Farris, A. B., Leopardi, F. V., Song, M., Stempora, L., … Cendales, L. C. (2015). Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates. Am J Transplant, 15(8), 2240–2249. https://doi.org/10.1111/ajt.13379
Freitas, A. M., K. P. Samy, A. B. Farris, F. V. Leopardi, M. Song, L. Stempora, E. A. Strobert, J. A. Jenkins, A. D. Kirk, and L. C. Cendales. “Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates.Am J Transplant 15, no. 8 (August 2015): 2240–49. https://doi.org/10.1111/ajt.13379.
Freitas AM, Samy KP, Farris AB, Leopardi FV, Song M, Stempora L, et al. Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates. Am J Transplant. 2015 Aug;15(8):2240–9.
Freitas, A. M., et al. “Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates.Am J Transplant, vol. 15, no. 8, Aug. 2015, pp. 2240–49. Pubmed, doi:10.1111/ajt.13379.
Freitas AM, Samy KP, Farris AB, Leopardi FV, Song M, Stempora L, Strobert EA, Jenkins JA, Kirk AD, Cendales LC. Studies Introducing Costimulation Blockade for Vascularized Composite Allografts in Nonhuman Primates. Am J Transplant. 2015 Aug;15(8):2240–2249.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

August 2015

Volume

15

Issue

8

Start / End Page

2240 / 2249

Location

United States

Related Subject Headings

  • Surgery
  • Primates
  • Neovascularization, Pathologic
  • Animals
  • Allografts
  • 3204 Immunology
  • 3202 Clinical sciences
  • 11 Medical and Health Sciences