TY - JOUR
T1 - Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors
AU - Deyle, David R.
AU - Escobar, Diana Zarate
AU - Peng, Kah Whye
AU - Babovic-Vuksanovic, Dusica
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Malignant peripheral nerve sheath tumors (MPNSTs) are devastating soft tissue sarcomas that can arise sporadically or in association with neurofibromatosis type I, have a poor prognosis, and have limited treatment options. Oncolytic measles virus therapy has been demonstrated to have significant antitumor properties in a number of different cancers, but the oncolytic potential of a MV Edmonston (MVEdm) vaccine strain engineered to express the human sodium iodide symporter (MV-NIS) on MPNST has not previously been evaluated. MPNST cell lines were found to highly express CD46, a cellular receptor required for measles viral entry, on their cell surface. After in vitro MV-NIS infection, MPNST cell lines showed significant cytopathic effect (CPE), while normal Schwann cells were less susceptible to CPE. Virus localization and distribution could be monitored by imaging of I-125 uptake. Local administration of MV-NIS into MPNST-derived tumors resulted in significant regression of tumor and improved survival. These results demonstrate feasibility of oncolytic measles virus therapy for MPNST patients and the possibility of a novel treatment for patients with NF1 tumors.
AB - Malignant peripheral nerve sheath tumors (MPNSTs) are devastating soft tissue sarcomas that can arise sporadically or in association with neurofibromatosis type I, have a poor prognosis, and have limited treatment options. Oncolytic measles virus therapy has been demonstrated to have significant antitumor properties in a number of different cancers, but the oncolytic potential of a MV Edmonston (MVEdm) vaccine strain engineered to express the human sodium iodide symporter (MV-NIS) on MPNST has not previously been evaluated. MPNST cell lines were found to highly express CD46, a cellular receptor required for measles viral entry, on their cell surface. After in vitro MV-NIS infection, MPNST cell lines showed significant cytopathic effect (CPE), while normal Schwann cells were less susceptible to CPE. Virus localization and distribution could be monitored by imaging of I-125 uptake. Local administration of MV-NIS into MPNST-derived tumors resulted in significant regression of tumor and improved survival. These results demonstrate feasibility of oncolytic measles virus therapy for MPNST patients and the possibility of a novel treatment for patients with NF1 tumors.
KW - Malignant peripheral nerve sheath tumor
KW - Measles virus
KW - Oncolytic therapy
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U2 - 10.1016/j.gene.2015.04.001
DO - 10.1016/j.gene.2015.04.001
M3 - Article
C2 - 25843626
AN - SCOPUS:84928431742
SN - 0378-1119
VL - 565
SP - 140
EP - 145
JO - Gene
JF - Gene
IS - 1
ER -