Interleukin 2-Bax: a novel prototype of human chimeric proteins for targeted therapy.
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.
Aqeilan
R
R
Department of Cellular Biochemistry and Human Genetics, Hebrew University-Hadassah Medical School, 91120, Jerusalem, Israel.
Yarkoni
S
S
Lorberboum-Galski
H
H
D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein