Characterization of the New Immune Suppressive Anti Human CD83 Monoclonal Antibody 3C12C in Non-Human Primates

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Abstract

Introduction

CD83 is a member of the Ig superfamily. It is membrane bound on activated dendritic cells (DC) and B cells. We developed a potential therapeutic human anti-human CD83 monoclonal antibody (3C12C) and showed it prevents graft versus host disease in a human PBMC mouse xenograft model. After establishing that 3C12C binds to non-human primate (NHP, baboon Papio Hamadryas) cells, we tested 3C12C in vivo in NHPs before a first in man, first in class, Phase I clinical trial.

Methods

Five baboons received 3C12C (1, 5, 10mg/kg, iv) or human IgG 10mg/kg on d0, 7, 14 and d21. Peripheral blood and serum were collected weekly (x4) then every 4 weeks (x2). Bone marrow and lymph node (LN) biopsies were taken at d28. Blood counts and biochemistry were monitored. Flow cytometry analysis followed the PBMC DC subsets, B cells and T cells and bone marrow haematopoietic stem cells. Immune histological studies were performed on LNs.

Results

All 5 animals remained well following anti-CD83 antibody injection. 3C12C did not change blood counts or liver function. CD4+T, CD8+T and B cells remained normal to d84. 3C12C injection increased peripheral Treg transiently at d21. 3C12C reduced blood CD1c+DC in a dose dependent manner. CD1c+DC were reduced in LN. 3C12C had no influence on bone marrow hematopoietic stem cell numbers.

Conclusion

Our results demonstrate that 3C12C is safe in NHPs and that it reduced activated DC numbers. This data will facilitate our planned Phase I trial of 3C12C in allogenic hematopoietic stem cell transplantation.

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