GBR-401 is a humanized anti-CD19 monoclonal antibody with high affinity for FcγRIIIa. It exhibits potent cytotoxicity in vitro and in vivo against various B-cell malignancies. GBR-401 induces cell death through antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxic effects. In severe combined immunodeficiency (SCID) mouse models with various xenografts, GBR-401 effectively eliminates malignant B cells and prolongs survival.

GBR-401 (0.00001-1 µg/mL, 4-24 h) exhibits significantly superior antibody-dependent cell-mediated cytotoxicity (ADCC) activity against malignant B cells, primary CLL, and lymphoma samples. The EC50 values for antibody-dependent cytotoxicity (ADCC) with GBR-401 in Raji, Ramos, SU-DHL-6, Namalwa, B-CLL, and Lymphoma cells are 1.2 ng/mL, 0.9 ng/mL, 0.8 ng/mL, 2 ng/mL, 1.6 ng/mL, and 15 ng/mL, respectively. Additionally, GBR-401 (0.1-5000 ng/mL, 2 h) rapidly increases the proportion of late apoptotic/necrotic cell death in Mec-1, Raji, and SU-DHL-6 cell lines. At a concentration of 1 μg/mL for 2 hours, GBR-401 initiates rapid and pronounced homotypic aggregation in Raji cells through actin reorganization, leading to cell death.

GBR-401, when administered intraperitoneally at doses ranging from 0.005 to 10 mg/kg in a single dose, induces B cell depletion in human PBMC xenograft mouse models. A single 2 mg/kg intraperitoneal dose of GBR-401 significantly reduces B-CLL cells in human CLL xenograft mouse models. Additionally, administration of GBR-401 at 2 mg/kg on days 3, 7, and 10 prolongs median survival time and enhances survival rates in mice with Raji cell xenografts.