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Nondepleting anti-CD40-based therapy prolongs allograft survival in nonhuman primates.
- Source :
-
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2012 Jan; Vol. 12 (1), pp. 126-35. Date of Electronic Publication: 2011 Sep 15. - Publication Year :
- 2012
-
Abstract
- Costimulation blockade of the CD40/CD154 pathway has been effective at preventing allograft rejection in numerous transplantation models. This strategy has largely depended on mAbs directed against CD154, limiting the potential for translation due to its association with thromboembolic events. Though targeting CD40 as an alternative to CD154 has been successful at preventing allograft rejection in preclinical models, there have been no reports on the effects of CD40-specific agents in human transplant recipients. This delay in clinical translation may in part be explained by the presence of cellular depletion with many CD40-specific mAbs. As such, the optimal biologic properties of CD40-directed immunotherapy remain to be determined. In this report, we have characterized 3A8, a human CD40-specific mAb and evaluated its efficacy in a rhesus macaque model of islet cell transplantation. Despite partially agonistic properties and the inability to block CD40 binding of soluble CD154 (sCD154) in vitro, 3A8-based therapy markedly prolonged islet allograft survival without depleting B cells. Our results indicate that the allograft-protective effects of CD40-directed costimulation blockade do not require sCD154 blockade, complete antagonism or cellular depletion, and serve to support and guide the continued development of CD40-specific agents for clinical translation.<br /> (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Subjects :
- Animals
Antibodies, Monoclonal immunology
CD40 Antigens immunology
Flow Cytometry
Immunotherapy
Lymphocyte Culture Test, Mixed
Macaca mulatta
Models, Animal
Antibodies, Monoclonal therapeutic use
CD40 Antigens antagonists & inhibitors
CD40 Ligand immunology
Graft Survival immunology
Islets of Langerhans Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1600-6143
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Publication Type :
- Academic Journal
- Accession number :
- 21920020
- Full Text :
- https://doi.org/10.1111/j.1600-6143.2011.03736.x