Monotherapy with anti-CD40 ligand antibody (IDEC 131) for non-human primate allograft heart transplantation

Pfeiffer, Steffen; Zorn, George L.; Azimzadeh, A.M.; Atkinson, Jeffrey J.; Newman, Roland; Pierson, Richard N.

doi:10.1016/s1053-2498(00)00568-4

Cited by 17 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously reported in this experimental series (12,29) and with another reagent (15), early graft cellular infiltration is typical in the setting of CD154 blocking monotherapy with IDEC-131 ( Fig. 2A).…”

Section: Graft Cellular Infiltration Under Cd154 Blockadesupporting

confidence: 86%

Alloimmunity in Primate Heart Recipients with CD154 Blockade: Evidence for Alternative Costimulation Mechanisms

Azimzadeh

Pfeiffer

et al. 2006

Transplantation

View full text Add to dashboard Cite

show abstract

Section: Graft Cellular Infiltration Under Cd154 Blockadesupporting

confidence: 86%

Alloimmunity in Primate Heart Recipients with CD154 Blockade: Evidence for Alternative Costimulation Mechanisms

Azimzadeh

Pfeiffer

et al. 2006

Transplantation

View full text Add to dashboard Cite

show abstract

“…However, the use of one of this anti-CD154 mAb-hu5C8-in human renal transplantation elicited thrombotic side effects that were also observed lately in NHPs (66), and thus precluded continued clinical trials. Anti-CD40 mAbs were similarly tested in the same species and prolonged the survival of islet and kidney allografts; however, long-term acceptance and true tolerance were not observed (67,68,69).…”

Section: Monoclonal Antibody or Fusion Protein Therapymentioning

confidence: 99%

The importance of large animal models in transplantation

Dehoux

Gianello²

2007

Front Biosci

View full text Add to dashboard Cite

Animal models have been extensively used in transplantation research. However, animal experimentation is contentious and subject to legal and ethical restrictions. Most experiments are carried out on rodents, but crucial prerequisites for the development of safe pre-clinical protocols in biomedical research are needed through suitable large animal models. In transplantation particularly, large animal models have developed dramatically. This article provides an overview of the large animal models commonly used to evaluate organ transplant experiments and analyzes the specificity of several models in various situations such as induction of allospecific tolerance and xenotransplantation. The key determination that remains be addressed is the most appropriate species and strains to model human immune and physiological systems. Because of their phylogenetic and physiologic similarities to man, non-human primates play an increasingly important role in pre-clinical testing. Nevertheless, a number of studies have shown the pig to be a reliable large animal model for transplantation research, and the availability of genetically defined or modified pigs establishes a stronger position for pigs as a large animal model.

show abstract

“…7, 23, 35 By using a directly comparable treatment regimen, here we show that both 5C8H1 and 2C10R4 significantly prolong cardiac allograft survival compared to historical IDEC-131 treated allografts. Additionally, 5C8H1 and 2C10R4 are each associated with improved control of pathogenic immunity, as demonstrated by reduced CAV severity scores during the second and third months of treatment and attenuation of alloAb development during treatment relative to IDEC-131, which is concordant with findings in several different NHP models using 5C8H1 or 2C10R4.…”

Section: Discussionmentioning

confidence: 68%

Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model

O’Neill

Braileanu²,

Sun³

et al. 2017

Transplantation

View full text Add to dashboard Cite

Background Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway. Methods Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized αCD154, n=9), 5C8H1 (mouse-human chimeric αCD154, n=5), or 2C10R4 (mouse-rhesus chimericαCD40, n=6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant. Results Relative to the previously reported IDEC-131 treated allografts, median survival time (MST 35±31 days) was significantly prolonged in both 5C8H1 (142±26, p<0.002) and 2C10R4 (124±37, p<0.020) treated allografts. IDEC-131 treated grafts had higher CAV severity scores during treatment relative to either 5C8H1 (p=0.008) or 2C10R4 (p=0.0002). Both 5C8H1(5 of 5 animals, p=0.02) and 2C10R4 (6/6, p=0.007), but not IDEC-131 (2/9), completely attenuated IgM antidonor alloAb production during treatment;5C8H1 (5/5) more consistently attenuated IgG alloAb production compared to 2C10R4 (4/6) and IDEC-131 (0/9). All evaluable explanted grafts experienced antibody-mediated rejection. Only 2C10R4 treated animals exhibited a modest, transient drop in CD20+ lymphocytes from baseline at d14 after transplant (-457±152 cells/μL) compared to 5C8H1 treated animals (16±25, p=0.037), and the resurgent B cells were primarily of a naïve phenotype. Conclusion In this model, CD154/CD40 axis blockade using IDEC-131 is an inferior immunomodulatory treatment than 5C8H1 or 2C10R4, which have similar efficacy to prolong graft survival and to delay CAV development and antidonor alloAb production during treatment.

show abstract

Monotherapy with anti-CD40 ligand antibody (IDEC 131) for non-human primate allograft heart transplantation

Cited by 17 publications

References 0 publications

Alloimmunity in Primate Heart Recipients with CD154 Blockade: Evidence for Alternative Costimulation Mechanisms

Alloimmunity in Primate Heart Recipients with CD154 Blockade: Evidence for Alternative Costimulation Mechanisms

The importance of large animal models in transplantation

Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model

Contact Info

Product

Resources

About