title: Bax345/BLyS: a novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin.
abstract: We generated a fusion protein Bax(345)/BLyS containing the truncated form of Bax (Bax(345)) at the N-terminus followed by a 218 linker to the B lymphocyte stimulator (BLyS). Bax(345)/BLyS was cytotoxic to a panel of diffuse large B cell lymphoma and mantle cell lymphoma lines expressing the BLyS receptors. Specific delivery of Bax(345)/BLyS to malignant B cells drove cells into apoptosis by mitochondrial dysfunction and treatment of cells with Bax(345)/BLyS induced down-regulation of Mcl-1, X-IAP, and survivin. Bax(345)/BLyS represents a new class of targeted therapeutic agents with a unique mechanism of action and may have therapeutic potential for malignant B cells.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Lyu
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Cheung
authors.forename: Walter N
authors.initials: WN
authors.lastname: Hittelman
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.forename: John W
authors.initials: JW
authors.lastname: Marks
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Cho
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenblum
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053264:B-Cell Activating Factor / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D023061:Gene Order; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020128:Inhibitory Concentration 50; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D053264:B-Cell Activating Factor; C574390:Bax345-BLyS fusion protein, human; D051034:Inhibitor of Apoptosis Proteins; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c