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Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()

Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these...

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Autores principales: Waters, Alicia M., Stafman, Laura L., Garner, Evan F., Mruthyunjayappa, Smitha, Stewart, Jerry E., Friedman, Gregory K., Coleman, Jennifer M., Markert, James M., Gillespie, G. Yancey, Beierle, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067929/
https://www.ncbi.nlm.nih.gov/pubmed/27751346
http://dx.doi.org/10.1016/j.tranon.2016.07.008
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author Waters, Alicia M.
Stafman, Laura L.
Garner, Evan F.
Mruthyunjayappa, Smitha
Stewart, Jerry E.
Friedman, Gregory K.
Coleman, Jennifer M.
Markert, James M.
Gillespie, G. Yancey
Beierle, Elizabeth A.
author_facet Waters, Alicia M.
Stafman, Laura L.
Garner, Evan F.
Mruthyunjayappa, Smitha
Stewart, Jerry E.
Friedman, Gregory K.
Coleman, Jennifer M.
Markert, James M.
Gillespie, G. Yancey
Beierle, Elizabeth A.
author_sort Waters, Alicia M.
collection PubMed
description Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ(1)34.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS.
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spelling pubmed-50679292016-10-24 Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma() Waters, Alicia M. Stafman, Laura L. Garner, Evan F. Mruthyunjayappa, Smitha Stewart, Jerry E. Friedman, Gregory K. Coleman, Jennifer M. Markert, James M. Gillespie, G. Yancey Beierle, Elizabeth A. Transl Oncol Original article Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ(1)34.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS. Neoplasia Press 2016-10-14 /pmc/articles/PMC5067929/ /pubmed/27751346 http://dx.doi.org/10.1016/j.tranon.2016.07.008 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Waters, Alicia M.
Stafman, Laura L.
Garner, Evan F.
Mruthyunjayappa, Smitha
Stewart, Jerry E.
Friedman, Gregory K.
Coleman, Jennifer M.
Markert, James M.
Gillespie, G. Yancey
Beierle, Elizabeth A.
Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title_full Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title_fullStr Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title_full_unstemmed Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title_short Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma()
title_sort effect of repeat dosing of engineered oncolytic herpes simplex virus on preclinical models of rhabdomyosarcoma()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067929/
https://www.ncbi.nlm.nih.gov/pubmed/27751346
http://dx.doi.org/10.1016/j.tranon.2016.07.008
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