TY - JOUR
T1 - Targeting polyIC to EGFR over-expressing cells using a dsRNA binding protein domain tethered to EGF
AU - Edinger, Nufar
AU - Lebendiker, Mario
AU - Klein, Shoshana
AU - Zigler, Maya
AU - Langut, Yael
AU - Levitzki, Alexander
N1 - Publisher Copyright:
© 2016 Edinger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/9
Y1 - 2016/9
N2 - Selective delivery of drugs to tumor cells can increase potency and reduce toxicity. In this study, we describe a novel recombinant chimeric protein, dsRBEC, which can bind polyIC and deliver it selectively into EGFR over-expressing tumor cells. dsRBEC, comprises the dsRNA binding domain (dsRBD) of human PKR (hPKR), which serves as the polyIC binding moiety, fused to human EGF (hEGF), the targeting moiety. dsRBEC shows high affinity towards EGFR and triggers ligand-induced endocytosis of the receptor, thus leading to the selective internalization of polyIC into EGFR over-expressing tumor cells. The targeted delivery of polyIC by dsRBEC induced cellular apoptosis and the secretion of IFN-β and other pro-inflammatory cytokines. dsRBEC-delivered polyIC is much more potent than naked polyIC and is expected to reduce the toxicity caused by systemic delivery of polyIC.
AB - Selective delivery of drugs to tumor cells can increase potency and reduce toxicity. In this study, we describe a novel recombinant chimeric protein, dsRBEC, which can bind polyIC and deliver it selectively into EGFR over-expressing tumor cells. dsRBEC, comprises the dsRNA binding domain (dsRBD) of human PKR (hPKR), which serves as the polyIC binding moiety, fused to human EGF (hEGF), the targeting moiety. dsRBEC shows high affinity towards EGFR and triggers ligand-induced endocytosis of the receptor, thus leading to the selective internalization of polyIC into EGFR over-expressing tumor cells. The targeted delivery of polyIC by dsRBEC induced cellular apoptosis and the secretion of IFN-β and other pro-inflammatory cytokines. dsRBEC-delivered polyIC is much more potent than naked polyIC and is expected to reduce the toxicity caused by systemic delivery of polyIC.
UR - http://www.scopus.com/inward/record.url?scp=84991256346&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0162321
DO - 10.1371/journal.pone.0162321
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 27598772
AN - SCOPUS:84991256346
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0162321
ER -
