UNASSIGNED: Otelixizumab is a monoclonal antibody (mAb) directed to @entity1 CD3  , a protein forming part of the CD3/T-cell receptor (TCR) complex on T lymphocytes. This study investigated the temporal interaction between varying concentrations of otelixizumab, binding to human CD3 antigen and expression of CD3/TCR complexes on lymphocytes in vitro, free from the confounding influence of changing lymphocyte frequencies observed in vivo. A static in vitro culture system was established in which primary @entity1 peripheral blood mononuclear cells (PBMCs) were incubated over an extended time course with titrated concentrations of otelixizumab. At each time point free, bound and total CD3/TCR expression on both @entity404 + and @entity405 + T cells and the amount of free otelixizuamb antibody in the supernatant were measured. The pharmacokinetics of free otelixizumab in the culture supernatants was saturable, with a shorter apparent half-life at low concentration. Correspondingly, a rapid, otelixizumab concentration and time-dependent reduction in CD3/TCR expression was observed. These combined observations were consistent with the phenomenon known as @entity734 ( @entity734 ). A mechanistic, mathematical pharmacokinetic/pharmacodynamic model was then used to characterize the free otelixizumab-CD3 expression-time relationship. CD3/TCR modulation induced by otelixizumab was found to be relatively fast as compared with re-expression rate of CD3/TCR complexes following otelixizumab removal from supernatants. In summary, the CD3/TCR receptor has been shown to have a major role in determining otelixizumab disposition. A mechanistic PK/ @entity1726 model successfully captured the PK and @entity1726 in vitro data, confirming @entity734 by otelixizumab.

The Temporal Pharmacokinetic-Pharmacodynamic Interaction between human CD3   antigen targeted monoclonal antibody Otelixizumab and CD3   binding and expression in XXXX Peripheral Blood Mononuclear Cell Static Culture.

@entity1 :: ('9606', 'Species') :: ['human'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity405 :: ('925', 'Gene') :: ['CD8'] @entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity734 :: ('MESH:D019966', 'Disease') :: ['target mediated drug disposition', 'TMDD']
@entity1 :: (9606,Species) :: ['Human']
