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

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• 作者：Mi-Ae Lyu^a ; Lawrence H. Cheung^a ; Walter N. Hittelman^a ; Yuying Liu^a ; John W. Marks^a ; Min-Jeong Cho^b ; Michael G. Rosenblum^a ; ^{mrosenbl@mdanderson.org}
• 关键词：Malignant B cells ; BLyS ; Bax ; Mitochondria ; Apoptosis
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 September, 2012
• 卷：322
• 期：2
• 页码：159-168
• 文件大小：1526 K

摘要

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.