Pharmacokinetics and pharmacodynamics of the cytolytic anti-CD38 human monoclonal antibody TAK-079 in monkey - model assisted preparation for the first in human trial.

ABSTRACT: We are studying the fully human, IgG1λ cytolytic monoclonal antibody TAK-079, which binds CD38. CD38 is expressed on plasma and natural killer (NK) cells constitutively and upregulated on subsets of B and T lymphocytes upon activation. TAK-079 cross-reacts with CD38 expressed by cynomolgus monkeys and depletes subsets of NK, B, and T cells. Therefore, safety and function of TAK-079 was evaluated in this species, prior to clinical development, using bioanalytical, and flow cytometry assays. We pooled the data from eight studies in healthy monkeys (dose range 0.03-100 mg/kg) and developed mathematical models that describe the pharmacokinetics and the exposure-effect relationship for NK cells, B cells, and T cells. NK cell depletion was identified as the most sensitive pharmacodynamic effect

SUBMITTER: Roepcke S 

PROVIDER: S-EPMC5980133 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature