Bax 345 /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...

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Bibliographic Details
Published in:Cancer letters 2012-09, Vol.322 (2), p.159
Main Authors: Mi-Ae Lyu, Cheung, Lawrence H, Hittelman, Walter N, Liu, Yuying, Marks, John W, Min-Jeong, Cho, Rosenblum, Michael G
Format: Article
Language:English
Subjects:
Apoptosis
Biological activity
Cell culture
Cytotoxicity
Drug resistance
Lymphoma
Mitochondria
Proteins
Tumors
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2012.02.029