@article{05579f3015214b72a6a8d3c48eb2e615,
title = "Multi-modal efficacy of a chimeric vesiculovirus expressing the Morreton glycoprotein in sarcoma",
abstract = "Vesiculoviruses are attractive oncolytic virus platforms due to their rapid replication, appreciable transgene capacity, broad tropism, limited preexisting immunity, and tumor selectivity through type I interferon response defects in malignant cells. We developed a synthetic chimeric virus (VMG) expressing the glycoprotein (G) from Morreton virus (MorV) and utilizing the remaining structural genes from vesicular stomatitis virus (VSV). VMG exhibited in vitro efficacy by inducing oncolysis in a broad range of sarcoma subtypes across multiple species. Notably, all cell lines tested showed the ability of VMG to yield productive infection with rapid replication kinetics and induction of apoptosis. Furthermore, pilot safety evaluations of VMG in immunocompetent, non-tumor-bearing mice showed an absence of toxicity with intranasal doses as high as 1e10 50% tissue culture infectious dose (TCID50)/kg. Locoregional administration of VMG in vivo resulted in tumor reduction in an immunodeficient Ewing sarcoma xenograft at doses as low as 2e5 TCID50. In a murine syngeneic fibrosarcoma model, while no tumor inhibition was achieved with VMG, there was a robust induction of CD8+ T cells within the tumor. The studies described herein establish the promising potential for VMG to be used as a novel oncolytic virotherapy platform with anticancer effects in sarcoma.",
keywords = "Morreton virus, oncolytics, sarcoma, vesiculovirus, virotherapy",
author = "Watters, {Chelsae R.} and Oumar Barro and Elliott, {Natalie M.} and Yumei Zhou and Musa Gabere and Elizabeth Raupach and Baker, {Alexander T.} and Barrett, {Michael T.} and Buetow, {Kenneth H.} and Bertram Jacobs and Mahesh Seetharam and Borad, {Mitesh J.} and Nagalo, {Bolni Marius}",
note = "Funding Information: M.J.B. has received grants to their institution from Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Five Prime Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceuticals, Boston Biomed, Basilea, Incyte Pharmaceuticals, Mirna Pharmaceuticals, Medimmune, Bioline, Sillajen, ARIAD Pharmaceuticals, PUMA Pharmaceuticals, Novartis Pharmaceuticals, QED Pharmaceuticals, and Pieris Pharmaceuticals; consultancy fees from ADC Therapeutics, Exelixis Pharmaceuticals, Inspyr Therapeutics, G1 Therapeutics, Immunovative Therapies, OncBioMune Pharmaceuticals, Western Oncolytics, and Lynx Group; and travel support from Astra Zeneca. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. M.J.B. and B.M.N. declare that they filed a patent application for the vectors and their derivatives included in this manuscript. Funding Information: We thank the personnel of the Department of Comparative Medicine at Mayo Clinic in Scottsdale, Arizona, for their assistance during animal studies. This work was supported by the National Institutes of Health (NIH) through a K01 award CA234324 (to B.M.N.); Marley Endowment Funds (Mayo Clinic Arizona) (to B.M.N.); National Cancer Institute (NCI) K12 award CA090628 (to M.J.B.); Hepatobiliary SPORE grant (to M.J.B.); Mayo Clinic Cancer Center CCSG Gene and Virus Therapy program grant (to M.J.B.); P50 grant CA210964 (to M.J.B. and B.M.N.); and a Department of Molecular Medicine (Mayo Clinic) Small Grant (to C.R.W.). Funding was also provided by the National Institute of Health (NIH) through a DP2 Award CA195764 (to M.J.B.) and start-up funds from the Winthrop P. Rockefeller Cancer Institute - UAMS (to B.M.N.). C.R.W. received a small grant from the Department of Molecular Medicine at Mayo Clinic. The graphical abstract was created with BioRender.com. Conceptualization, C.R.W. M.J.B. and B.M.N.; methodology, C.R.W. O.B. A.T.B. Y.Z. M.J.B. and B.M.N.; investigation, C.R.W.; visualization, C.R.W.; writing – original draft, C.R.W.; writing – review & editing, C.R.W. O.B. N.M.E. A.T.B. M.G. E.R. M.T.B. K.H.B. B.J. M.J.B. and B.M.N; funding acquisition, C.R.W. M.S. M.J.B. and B.M.N; resources, M.J.B. and B.M.N.; supervision, M.J.B. and B.M.N. All co-authors have seen and agree with the contents of the manuscript. M.J.B. has received grants to their institution from Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Five Prime Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceuticals, Boston Biomed, Basilea, Incyte Pharmaceuticals, Mirna Pharmaceuticals, Medimmune, Bioline, Sillajen, ARIAD Pharmaceuticals, PUMA Pharmaceuticals, Novartis Pharmaceuticals, QED Pharmaceuticals, and Pieris Pharmaceuticals; consultancy fees from ADC Therapeutics, Exelixis Pharmaceuticals, Inspyr Therapeutics, G1 Therapeutics, Immunovative Therapies, OncBioMune Pharmaceuticals, Western Oncolytics, and Lynx Group; and travel support from Astra Zeneca. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. M.J.B. and B.M.N. declare that they filed a patent application for the vectors and their derivatives included in this manuscript. Funding Information: We thank the personnel of the Department of Comparative Medicine at Mayo Clinic in Scottsdale, Arizona, for their assistance during animal studies. This work was supported by the National Institutes of Health (NIH) through a K01 award CA234324 (to B.M.N.); Marley Endowment Funds (Mayo Clinic Arizona) (to B.M.N.); National Cancer Institute (NCI) K12 award CA090628 (to M.J.B.); Hepatobiliary SPORE grant (to M.J.B.); Mayo Clinic Cancer Center CCSG Gene and Virus Therapy program grant (to M.J.B.); P50 grant CA210964 (to M.J.B. and B.M.N.); and a Department of Molecular Medicine (Mayo Clinic) Small Grant (to C.R.W.). Funding was also provided by the National Institute of Health (NIH) through a DP2 Award CA195764 (to M.J.B.) and start-up funds from the Winthrop P. Rockefeller Cancer Institute - UAMS (to B.M.N.). C.R.W. received a small grant from the Department of Molecular Medicine at Mayo Clinic. The graphical abstract was created with BioRender.com . Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = jun,
day = "15",
doi = "10.1016/j.omto.2023.02.009",
language = "English (US)",
volume = "29",
pages = "4--14",
journal = "Molecular Therapy - Oncolytics",
issn = "2372-7705",
publisher = "Nature Publishing Group",
}