Bax345/BLyS: A novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin

We generated a fusion protein Bax345/BLyS containing the truncated form of Bax (Bax345) at the N-terminus followed by a 218 linker to the B lymphocyte stimulator (BLyS). Bax345/BLyS was cytotoxic to a panel of diffuse large B cell lymphoma and mantle cell lymphoma lines expressing the BLyS receptors. Specific delivery of Bax345/BLyS to malignant B cells drove cells into apoptosis by mitochondrial dysfunction and treatment of cells with Bax345/BLyS induced down-regulation of Mcl-1, X-IAP, and survivin. Bax345/BLyS represents a new class of targeted therapeutic agents with a unique mechanism of action and may have therapeutic potential for malignant B cells.