TY - JOUR
T1 - Apoptosis-inducing human-origin Fcε-Bak chimeric proteins for targeted elimination of mast cells and basophils
T2 - A new approach for allergy treatment
AU - Belostotsky, R.
AU - Lorberboum-Galski, H.
PY - 2001/10/15
Y1 - 2001/10/15
N2 - During the past few years, many chimeric proteins have been developed to specifically target and kill cells expressing specific surface molecules. Generally these molecules carry a bacterial or plant toxin to destroy the unwanted cells. The major obstacle regarding these molecules in their clinical application is the immunogenicity and nonspecific toxicity associated with bacterial or plant toxins. We lately reported a new approach for construction of chimeric proteins: We successfully replaced bacterial or plant toxins with human apoptosis-inducing proteins. The resulting chimeras were shown to specifically induce apoptosis in the target cells. Taking advantage of the human apoptosis inducing proteins Bak and Bax as novel killing components, we have now constructed new chimeric proteins targeted against the human FcεRI, expressed mainly on mast cells and basophils. These cells are the main effectors of the allergic response. Treatment of the target cells with the new chimeric proteins, termed Fcε-Bak/Bax, had a dramatic effect on cell survival, causing apoptosis. The effect was specific to cells expressing the FcεRI of both human and, very unexpectedly, also of mouse origin. Moreover, interaction of the chimeric proteins with the mast cells did not cause degranulation. Fcε-Bak/Bax are new chimeric proteins of human origin and, as such, are expected to be both less immunogenic and less toxic and, thus, may be specific and efficient reagents for the treatment of allergic diseases.
AB - During the past few years, many chimeric proteins have been developed to specifically target and kill cells expressing specific surface molecules. Generally these molecules carry a bacterial or plant toxin to destroy the unwanted cells. The major obstacle regarding these molecules in their clinical application is the immunogenicity and nonspecific toxicity associated with bacterial or plant toxins. We lately reported a new approach for construction of chimeric proteins: We successfully replaced bacterial or plant toxins with human apoptosis-inducing proteins. The resulting chimeras were shown to specifically induce apoptosis in the target cells. Taking advantage of the human apoptosis inducing proteins Bak and Bax as novel killing components, we have now constructed new chimeric proteins targeted against the human FcεRI, expressed mainly on mast cells and basophils. These cells are the main effectors of the allergic response. Treatment of the target cells with the new chimeric proteins, termed Fcε-Bak/Bax, had a dramatic effect on cell survival, causing apoptosis. The effect was specific to cells expressing the FcεRI of both human and, very unexpectedly, also of mouse origin. Moreover, interaction of the chimeric proteins with the mast cells did not cause degranulation. Fcε-Bak/Bax are new chimeric proteins of human origin and, as such, are expected to be both less immunogenic and less toxic and, thus, may be specific and efficient reagents for the treatment of allergic diseases.
UR - http://www.scopus.com/inward/record.url?scp=0035887634&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.167.8.4719
DO - 10.4049/jimmunol.167.8.4719
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C2 - 11591803
AN - SCOPUS:0035887634
SN - 0022-1767
VL - 167
SP - 4719
EP - 4728
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -