Bax 345/BLyS: A novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin

Mi Ae Lyu; Lawrence H. Cheung; Walter N. Hittelman; Yuying Liu; John W. Marks; Min Jeong Cho; Michael G. Rosenblum

doi:10.1016/j.canlet.2012.02.029

Bax ₃₄₅/BLyS: A novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin

Mi Ae Lyu
, Lawrence H. Cheung
, Walter N. Hittelman
, Yuying Liu
, John W. Marks
, Min Jeong Cho
, Michael G. Rosenblum

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Pages (from-to)	159-168
Number of pages	10
Journal	Cancer Letters
Volume	322
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2012.02.029
State	Published - Sep 28 2012

Keywords

Apoptosis
BLyS
Bax
Malignant B cells
Mitochondria

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.canlet.2012.02.029

Cite this

@article{7424041ebf274fe289d5c842f5c670c0,

title = "Bax 345/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.",

keywords = "Apoptosis, BLyS, Bax, Malignant B cells, Mitochondria",

author = "Lyu, \{Mi Ae\} and Cheung, \{Lawrence H.\} and Hittelman, \{Walter N.\} and Yuying Liu and Marks, \{John W.\} and Cho, \{Min Jeong\} and Rosenblum, \{Michael G.\}",

note = "Funding Information: This research was conducted, in part, by the Clayton Foundation for Research (MGR)",

year = "2012",

month = sep,

day = "28",

doi = "10.1016/j.canlet.2012.02.029",

language = "English (US)",

volume = "322",

pages = "159--168",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

T1 - Bax 345/BLyS

T2 - A novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin

AU - Lyu, Mi Ae

AU - Cheung, Lawrence H.

AU - Hittelman, Walter N.

AU - Liu, Yuying

AU - Marks, John W.

AU - Cho, Min Jeong

AU - Rosenblum, Michael G.

N1 - Funding Information: This research was conducted, in part, by the Clayton Foundation for Research (MGR)

PY - 2012/9/28

Y1 - 2012/9/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - BLyS

KW - Bax

KW - Malignant B cells

KW - Mitochondria

UR - https://www.scopus.com/pages/publications/84861682829

UR - https://www.scopus.com/pages/publications/84861682829#tab=citedBy

U2 - 10.1016/j.canlet.2012.02.029

DO - 10.1016/j.canlet.2012.02.029

M3 - Article

C2 - 22388102

AN - SCOPUS:84861682829

SN - 0304-3835

VL - 322

SP - 159

EP - 168

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -