Phenotypical Analysis after Administration of Anti-HLA ClassII-DR Humanized Monoclonal Antibody, IMMU-114 in Non-Human Primate

Abstract

Background: Anti-HLA classII-DR humanized monoclonal antibody, IMMU-114 depletes HLA-DR positive cells by inducing apoptosis. To apply IMMU-114 for human trial, studies in non-human primate model is mandatory. The phenotypical changes of peripheral blood mononuclear cells (PBMCs) by IMMU-114 administration were investigated by flowcytemtery in monkey. Methods: IMMU-114 at a dose of 3 mg/kg was given intravenously, to two crab-eating monkeys, weighing 3-4 kg. PBMCs were obtained before (Pre) and 7 days (D7) after IMMU-114 administration, and analyzed by flowcytemtry. Results were expressed as the mean frequency of antigen-positive cells, in order of Pre vs. D7. Results: HLA-DR+ cells were 14.2 vs. 14.7%. CD3+CD25+ T cells were 2.5 vs. 6.2%. CD4+CD25+ T cells were 5.0 vs. 8.9%. CD8+CD25+ T cells were 8.8 vs. 9.6%. CD20+ B cells were 18.7 vs. 16.8%, and CD20+HLA-DR+ B cells were 14.8 vs. 13.0%. CD16+ NK cells were 17.9 vs. 11.6% and CD16+ HLA-DR+ NK cells were 5.4% vs. 2.35%. CD14+ macrophages were 12.8 vs. 8.7%, and CD14+ HLA-DR+ macrophages were 8.5% vs. 3.5%. Conclusions: IMMU-114, at a dose of 3 mg/kg had mild effects on decreasing the frequency of HLA-DR-expressing B cells, NK cells, and macrophages in mokey. However, the deletion of HLA-DR-expressing cells was mild, increasing the dose or repeated administration of IMMU-114 are required in non-human primates model.