A novel tumor-bearing humanized mouse model for evaluating the efficacy and predictive safety of bispecific T cell engager

Abstract Bispecific T cell engager (BiTE) is one of the most promising therapeutic approaches for treatment various malignancies. Humanized mice engrafted with human peripheral blood mononuclear cells (PBMCs) have currently become preclinical platform evaluating effectiveness cancer immunotherapies including BiTE. However, wide application this humanized animal model limited by a strong xenoreaction against mouse tissues. In study, we used murine major histocompatibility class I and II double knock-out NSG (referred to DKO) evaluate antitumor effect The DKO were implanted pre-B acute lymphoblastic leukemia line (Nalm6). Five days later, reconstituted PBMCs. Following CD19xCD3 BiTE whole-body tumor burden was quantified in vivo imaging system. Our data demonstrated that developed consistent clinical signs leukemia-related body weight loss hind-limb paralysis within 4 weeks. With serial dose treatment, growing significantly suppressed. A lower incidence prolonged survival observed BiTE-treated compared controls. addition, after BiTE, exhibited elevated serum levels IFN-γ, TNF-a, IL-6, IL-10, IL-2, IL-4. cytokine production dose-dependent associated increase effectiveness. This tumor-bearing provides efficacy, toxic release, dosing requirements any cell-based treatment.