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

Published

Journal Article

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 Therapy was withdrawn after 3 months.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.

Full Text

Duke Authors

Cited Authors

  • Preston, EH; Xu, H; Dhanireddy, KK; Pearl, JP; Leopardi, FV; Starost, MF; Hale, DA; Kirk, AD

Published Date

  • May 2005

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • 1032 - 1041

PubMed ID

  • 15816883

Pubmed Central ID

  • 15816883

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2005.00796.x

Language

  • eng

Conference Location

  • United States