Interleukin 2‐Bax: a novel prototype of human chimeric proteins for targeted therapy

FEBS Letters

Aqeilan, Rami¹  Lorberboum-Galski, Haya¹  Yarkoni, Shai¹ 

[1] Department of Cellular Biochemistry and Human Genetics, Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel

关键词: Interleukin 2;    Bax;    Apoptosis;    Targeted therapy;    Chimeric protein;   

DOI  :  10.1016/S0014-5793(99)01050-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

During the past few years many chimeric proteins have been developed to target and kill cells expressing specific surface molecules. Generally, these molecules carry a bacterial or plant toxin that destroys the unwanted cells. The major obstacle in the clinical application of such chimeras is their immunogenicity and non-specific toxicity. We have developed a new generation of chimeric proteins, taking advantage of apoptosis-inducing proteins, such as the human Bax protein, as novel killing components. The first prototype chimeric protein, IL2-Bax, directed toward IL2R-expressing cells, was constructed, expressed in Escherichia coli and partially purified. IL2-Bax increased the population of apoptotic cells in a variety of target T cell lines, as well as in human fresh PHA-activated lymphocytes, in a dose-dependent manner and had no effect on cells lacking IL2R expression. The IL2-Bax chimera represents an innovative approach for constructing chimeric proteins comprising a molecule that binds a specific cell type and an apoptosis-inducing protein. Such new chimeric proteins could be used for targeted treatment of human diseases.

【 授权许可】

Unknown