Peripheral Blood Mononuclear Cell (PBMC) Humanized Mice as a Platform for a Preclinical In Vivo Evaluation of T-Cell-Dependent Bispecific Antibodies.

Amid advancements in antibody-based cancer immunotherapy, T-cell-dependent bispecific antibodies (TDBs) hold great promise in cancer treatment. Peripheral blood mononuclear cell (PBMC) humanized mice serve as a platform for preclinical characterization of TDBs, although its induction of xenogeneic graft-versus-host disease (GvHD) limits the experimental time window and introduces confounding factors. NSG-MHC I/II DKO mouse is a highly immunodeficient mouse knocked out for mouse MHC class I and II molecules, which delay GvHD onset following human PBMC engraftment. Here, we describe the materials and methods for generating PBMC humanized mouse models with NSG-MHC I/II DKO mice. Using this model, we demonstrate the feasibility of testing the in vivo efficacy of TDBs in NSG-MHC I/II DKO mice engrafted with the colorectal cancer cell line HT29.