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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

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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ICMJE
MLA
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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
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