TY - JOUR
T1 - Development of novel promiscuous anti-chemokine peptibodies for treating autoimmunity and inflammation
AU - Abraham, Michal
AU - Wald, Hanna
AU - Vaizel-Ohayon, Dalit
AU - Grabovsky, Valentin
AU - Oren, Zohar
AU - Karni, Arnon
AU - Weiss, Lola
AU - Galun, Eithan
AU - Peled, Amnon
AU - Eizenberg, Orly
N1 - Publisher Copyright:
© 2017 Abraham, Wald, Vaizel-Ohayon, Grabovsky, Oren, Karni, Weiss, Galun, Peled and Eizenberg.
PY - 2017/11/23
Y1 - 2017/11/23
N2 - Chemokines and their receptors play critical roles in the progression of autoimmunity and inflammation. Typically, multiple chemokines are involved in the development of these pathologies. Indeed, targeting single chemokines or chemokine receptors has failed to achieve significant clinical benefits in treating autoimmunity and inflammation. Moreover, the binding of host atypical chemokine receptors to multiple chemokines as well as the binding of chemokine-binding proteins secreted by various pathogens can serve as a strategy for controlling inflammation. In this work, promiscuous chemokine-binding peptides that could bind and inhibit multiple inflammatory chemokines, such as CCL2, CCL5, and CXCL9/10/11, were selected from phage display libraries. These peptides were cloned into human mutated immunoglobulin Fc-protein fusions (peptibodies). The peptibodies BKT120Fc and BKT130Fc inhibited the ability of inflammatory chemokines to induce the adhesion and migration of immune cells. Furthermore, BKT120Fc and BKT130Fc also showed a significant inhibition of disease progression in a variety of animal models for autoimmunity and inflammation. Developing a novel class of antagonists that can control the courses of diseases by selectively blocking multiple chemokines could be a novel way of generating effective therapeutics.
AB - Chemokines and their receptors play critical roles in the progression of autoimmunity and inflammation. Typically, multiple chemokines are involved in the development of these pathologies. Indeed, targeting single chemokines or chemokine receptors has failed to achieve significant clinical benefits in treating autoimmunity and inflammation. Moreover, the binding of host atypical chemokine receptors to multiple chemokines as well as the binding of chemokine-binding proteins secreted by various pathogens can serve as a strategy for controlling inflammation. In this work, promiscuous chemokine-binding peptides that could bind and inhibit multiple inflammatory chemokines, such as CCL2, CCL5, and CXCL9/10/11, were selected from phage display libraries. These peptides were cloned into human mutated immunoglobulin Fc-protein fusions (peptibodies). The peptibodies BKT120Fc and BKT130Fc inhibited the ability of inflammatory chemokines to induce the adhesion and migration of immune cells. Furthermore, BKT120Fc and BKT130Fc also showed a significant inhibition of disease progression in a variety of animal models for autoimmunity and inflammation. Developing a novel class of antagonists that can control the courses of diseases by selectively blocking multiple chemokines could be a novel way of generating effective therapeutics.
KW - Autoimmunity
KW - Chemokines
KW - Inflammation
KW - Peptibodies
KW - Phage display
UR - http://www.scopus.com/inward/record.url?scp=85034998798&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01432
DO - 10.3389/fimmu.2017.01432
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AN - SCOPUS:85034998798
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - NOV
M1 - 1432
ER -