Evaluation of the Ability of Immune Humanized Mice to Demonstrate CD20-Specific Cytotoxicity Induced by Ofatumumab.

ABSTRACT: CD20 monoclonal antibodies are well-established therapeutics for the treatment of B-cell malignancies. Several mechanisms of target cell killing occur from anti-CD20 therapy, including complement-dependent cytotoxicity (CDC) cell lysis and antibody-dependent cell-mediated cytotoxicity. Human Fc receptors (FcRs) are required to mediate these functions and are either not present or not cross-reactive in mice and most animal species. In contrast, some nonhuman primates have cross-reactive FcR; however, their cellular expression and function may differ from humans. Therefore, we tested bone marrow-liver-thymus (BLT) humanized mice to determine if they could recapitulate the pharmacokinetics (PKs), pharmacodynamics, and potential toxicities of ofatumumab, for which CDC is the predominant mechan

SUBMITTER: Semple KM 

PROVIDER: S-EPMC6510375 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature