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IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates.

Publication ,  Journal Article
Preston, EH; Xu, H; Dhanireddy, KK; Pearl, JP; Leopardi, FV; Starost, MF; Hale, DA; Kirk, AD
Published in: Am J Transplant
May 2005

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.

Duke Scholars

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

May 2005

Volume

5

Issue

5

Start / End Page

1032 / 1041

Location

United States

Related Subject Headings

  • Time Factors
  • TOR Serine-Threonine Kinases
  • Surgery
  • Skin Transplantation
  • Sirolimus
  • Protein Kinases
  • Primates
  • Major Histocompatibility Complex
  • Macaca mulatta
  • Lymphocytes
 

Citation

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Preston, E. H., Xu, H., Dhanireddy, K. K., Pearl, J. P., Leopardi, F. V., Starost, M. F., … Kirk, A. D. (2005). IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates. Am J Transplant, 5(5), 1032–1041. https://doi.org/10.1111/j.1600-6143.2005.00796.x
Preston, Edwin H., He Xu, Kiran K. Dhanireddy, Jonathan P. Pearl, Frank V. Leopardi, Matthew F. Starost, Douglas A. Hale, and Allan D. Kirk. “IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates.Am J Transplant 5, no. 5 (May 2005): 1032–41. https://doi.org/10.1111/j.1600-6143.2005.00796.x.
Preston EH, Xu H, Dhanireddy KK, Pearl JP, Leopardi FV, Starost MF, et al. IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates. Am J Transplant. 2005 May;5(5):1032–41.
Preston, Edwin H., et al. “IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates.Am J Transplant, vol. 5, no. 5, May 2005, pp. 1032–41. Pubmed, doi:10.1111/j.1600-6143.2005.00796.x.
Preston EH, Xu H, Dhanireddy KK, Pearl JP, Leopardi FV, Starost MF, Hale DA, Kirk AD. IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates. Am J Transplant. 2005 May;5(5):1032–1041.
Journal cover image

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

May 2005

Volume

5

Issue

5

Start / End Page

1032 / 1041

Location

United States

Related Subject Headings

  • Time Factors
  • TOR Serine-Threonine Kinases
  • Surgery
  • Skin Transplantation
  • Sirolimus
  • Protein Kinases
  • Primates
  • Major Histocompatibility Complex
  • Macaca mulatta
  • Lymphocytes