BACKGROUND: The CD40/CD154 and CD28/B7 pathways are important in allo- and xeno-transplantation. Owing to the thrombotic complications of anti-CD154mAb, anti-CD40mAb has emerged as a promising inhibitor of costimulation. Various clones of anti-CD40mAb have been developed against primate species, e.g., clone 2C10 against rhesus monkeys. We have compared the in vitro efficacy of 2C10 to prevent a T cell response in primates and pigs. METHODS: The binding of 2C10 to antigen-presenting cells (PBMCs [B cells]) of humans, rhesus and cynomolgus monkeys, baboons, and pigs was measured by flow cytometry, and was also tested indirectly by a blocking assay. The functional capacity of 2C10 was tested by mixed lymphocyte reaction (MLR) with polyclonal stimulation by phytohemagglutinin (PHA) and also with wild-type pig aortic endothelial cells (pAECs) as stimulators. RESULTS: There was a significant reduction in binding of 2C10 to baboon PBMCs compared to rhesus, cynomolgus, and human PBMCs, and minimal binding to pig PBMCs. The blocking assay confirmed that the binding of 2C10 was significantly lower to baboon PBMCs when compared to the other primate species tested. The functional assay with PHA showed significantly reduced inhibition of PBMC proliferation in humans, cynomolgus monkeys, and baboons compared to rhesus monkeys, which was confirmed on MLR with pAECs. CONCLUSIONS: Since both the binding and functional activity of 2C10 in the baboon is lower than in rhesus monkeys, in vivo treatment using 2C10 in the baboon might require a higher dose or more frequent administration in comparison to rhesus monkeys. It may also be beneficial to develop species-specific clones of anti-CD40mAb.
BACKGROUND: The CD40/CD154 and CD28/B7 pathways are important in allo- and xeno-transplantation. Owing to the thrombotic complications of anti-CD154mAb, anti-CD40mAb has emerged as a promising inhibitor of costimulation. Various clones of anti-CD40mAb have been developed against primate species, e.g., clone 2C10 against rhesus monkeys. We have compared the in vitro efficacy of 2C10 to prevent a T cell response in primates and pigs. METHODS: The binding of 2C10 to antigen-presenting cells (PBMCs [B cells]) of humans, rhesus and cynomolgus monkeys, baboons, and pigs was measured by flow cytometry, and was also tested indirectly by a blocking assay. The functional capacity of 2C10 was tested by mixed lymphocyte reaction (MLR) with polyclonal stimulation by phytohemagglutinin (PHA) and also with wild-type pig aortic endothelial cells (pAECs) as stimulators. RESULTS: There was a significant reduction in binding of 2C10 to baboon PBMCs compared to rhesus, cynomolgus, and human PBMCs, and minimal binding to pig PBMCs. The blocking assay confirmed that the binding of 2C10 was significantly lower to baboon PBMCs when compared to the other primate species tested. The functional assay with PHA showed significantly reduced inhibition of PBMC proliferation in humans, cynomolgus monkeys, and baboons compared to rhesus monkeys, which was confirmed on MLR with pAECs. CONCLUSIONS: Since both the binding and functional activity of 2C10 in the baboon is lower than in rhesus monkeys, in vivo treatment using 2C10 in the baboon might require a higher dose or more frequent administration in comparison to rhesus monkeys. It may also be beneficial to develop species-specific clones of anti-CD40mAb.
Authors: Christian P Larsen; Josep Grinyó; José Medina-Pestana; Yves Vanrenterghem; Flavio Vincenti; Barbara Breshahan; Josep M Campistol; Sander Florman; Maria del Carmen Rial; Nassim Kamar; Alan Block; Gregory Di Russo; Chen-Sheng Lin; Pushkal Garg; Bernard Charpentier Journal: Transplantation Date: 2010-12-27 Impact factor: 4.939
Authors: Burcin Ekser; Mohamed Ezzelarab; Hidetaka Hara; Dirk J van der Windt; Martin Wijkstrom; Rita Bottino; Massimo Trucco; David K C Cooper Journal: Lancet Date: 2011-10-20 Impact factor: 79.321
Authors: A Page; S Srinivasan; K Singh; M Russell; K Hamby; T Deane; S Sen; L Stempora; F Leopardi; A A Price; E Strobert; K A Reimann; A D Kirk; C P Larsen; L S Kean Journal: Am J Transplant Date: 2011-09-19 Impact factor: 8.086
Authors: Tadatsura Koshika; Carol Phelps; Jason Fang; Seung Eun Lee; Minoru Fujita; David Ayares; David K C Cooper; Hidetaka Hara Journal: Immunology Date: 2011-12 Impact factor: 7.397
Authors: Hidetaka Hara; Naoko Koike; Cassandra Long; Jordan Piluek; Danny S Roh; Nirmala SundarRaj; James L Funderburgh; Yoshiaki Mizuguchi; Kumiko Isse; Carol J Phelps; Suyapa F Ball; David L Ayares; David K C Cooper Journal: Invest Ophthalmol Vis Sci Date: 2011-07-15 Impact factor: 4.799
Authors: P Thompson; K Cardona; M Russell; I R Badell; V Shaffer; G Korbutt; G R Rayat; J Cano; M Song; W Jiang; E Strobert; R Rajotte; T Pearson; A D Kirk; C P Larsen Journal: Am J Transplant Date: 2011-05 Impact factor: 8.086
Authors: T Aoyagi; K Yamashita; T Suzuki; M Uno; R Goto; M Taniguchi; T Shimamura; N Takahashi; T Miura; K Okimura; T Itoh; A Shimizu; H Furukawa; S Todo Journal: Am J Transplant Date: 2009-06-10 Impact factor: 8.086
Authors: Hidetaka Hara; Cassandra Long; Yih Jyh Lin; Hao-Chih Tai; Mohamed Ezzelarab; David Ayares; David K C Cooper Journal: Transpl Int Date: 2008-09-01 Impact factor: 3.782