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CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates.

Publication ,  Journal Article
Thompson, P; Cardona, K; Russell, M; Badell, IR; Shaffer, V; Korbutt, G; Rayat, GR; Cano, J; Song, M; Jiang, W; Strobert, E; Rajotte, R ...
Published in: Am J Transplant
May 2011

The widespread clinical implementation of alloislet transplantation as therapy for type 1 diabetes has been hindered by the lack of suitable islet donors. Pig-to-human islet xenotransplantation is one strategy with potential to alleviate this shortage. Long-term survival of porcine islets has been achieved using CD154-specific antibodies to interrupt the CD40/CD154 costimulation pathway; however, CD154-specific antibodies seem unlikely candidates for clinical translation. An alternative strategy for CD40/CD154 pathway interruption is use of CD40-specific antibodies. Herein, we evaluate the ability of a chimeric CD40-specific monoclonal antibody (Chi220) to protect islet xenografts. Neonatal porcine islets (~50,000 IEQ/kg) were transplanted intraportally into pancreatectomized diabetic macaques. Immunosuppression consisted of induction therapy with Chi220 and the IL-2 receptor-specific antibody basiliximab, and maintenance therapy with sirolimus and the B7-specific fusion protein belatacept. Chi220 effectively promoted xenoislet engraftment and survival, with five of six treated recipients achieving insulin-independent normoglycemia (median rejection-free survival 59 days; mean 90.8 days, maximum 203 days). No thromboembolic phenomena were observed. CD40 represents a promising alternative to CD154 as a therapeutic target, and the efficacy of CD40-specific antibodies in islet xenotransplantation warrants further investigation.

Duke Scholars

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Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

May 2011

Volume

11

Issue

5

Start / End Page

947 / 957

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Sirolimus
  • Recombinant Fusion Proteins
  • Receptors, Interleukin-2
  • Primates
  • Male
  • Macaca mulatta
  • Islets of Langerhans Transplantation
 

Citation

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Thompson, P., Cardona, K., Russell, M., Badell, I. R., Shaffer, V., Korbutt, G., … Larsen, C. P. (2011). CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant, 11(5), 947–957. https://doi.org/10.1111/j.1600-6143.2011.03509.x
Thompson, P., K. Cardona, M. Russell, I. R. Badell, V. Shaffer, G. Korbutt, G. R. Rayat, et al. “CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates.Am J Transplant 11, no. 5 (May 2011): 947–57. https://doi.org/10.1111/j.1600-6143.2011.03509.x.
Thompson P, Cardona K, Russell M, Badell IR, Shaffer V, Korbutt G, et al. CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant. 2011 May;11(5):947–57.
Thompson, P., et al. “CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates.Am J Transplant, vol. 11, no. 5, May 2011, pp. 947–57. Pubmed, doi:10.1111/j.1600-6143.2011.03509.x.
Thompson P, Cardona K, Russell M, Badell IR, Shaffer V, Korbutt G, Rayat GR, Cano J, Song M, Jiang W, Strobert E, Rajotte R, Pearson T, Kirk AD, Larsen CP. CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant. 2011 May;11(5):947–957.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

May 2011

Volume

11

Issue

5

Start / End Page

947 / 957

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Sirolimus
  • Recombinant Fusion Proteins
  • Receptors, Interleukin-2
  • Primates
  • Male
  • Macaca mulatta
  • Islets of Langerhans Transplantation