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 - Funding Information:
The authors thank Nancy Ratner (Cincinnati Children's Hospital Medical Center) and Margaret R. Wallace (University of Florida) for providing normal Schwann cell lines and technical advice and David A. Largaespada (University of Minnesota) for providing MPNST cell lines. This work was supported by the Mayo Clinic Foundation Small Grant Program for D.R.D. and K.W.P.
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 -