Characterization of the New Immune Suppressive Anti Human CD83 Monoclonal Antibody 3C12C in Non-Human Primates
Xinsheng Ju1,2, Christian E Bryant1,3, Suzanne Pears4, Neroli Sunderland4, Scott Heffernan4, Annemarie Hennessy4, Phillip D Fromm1,2, Kenneth Lee2,5, Candice Clarke2, Pablo A Silveira1,2, Con Tsonis1, Georgina J Clark1,2, Derek NJ Hart1,2.
1Dendritic Cell Research, ANZAC Research Institute, Sydney, Australia; 2Sydney Medical School, The University of Sydney, Sydney, Australia; 3Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, Australia; 4Animal Facility, Royal Prince Alfred Hospital, Camperdown, Australia; 5Anatomical Pathology, Concord Repatriation General Hospital, Sydney, Australia
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.
