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In vitro testing of an anti-CD40 monoclonal antibody, clone 2C10, in primates and pigs. Transpl Immunol 2015 Nov;33(3):185-91

Date

10/16/2015

Pubmed ID

26458513

Pubmed Central ID

PMC4648655

DOI

10.1016/j.trim.2015.09.007

Scopus ID

2-s2.0-84947613593   6 Citations

Abstract

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.

Author List

Lee W, Satyananda V, Iwase H, Tanaka T, Miyagawa Y, Long C, Ayares D, Cooper DK, Hara H

Author

Whayoung Lee MD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
B-Lymphocytes
CD40 Antigens
Cell Proliferation
Cells, Cultured
Coculture Techniques
Disease Models, Animal
Endothelium, Vascular
Graft Rejection
Humans
Lymphocyte Culture Test, Mixed
Primates
Swine
T-Lymphocytes