@article{43eee94c29424a1692cc29fa7239623d,
title = "Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers",
abstract = "Background: Morreton virus (MORV) is an oncolytic Vesiculovirus, genetically distinct from vesicular stomatitis virus (VSV). Aim: To report that MORV induced potent cytopathic effects (CPEs) in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) in vitro models. Approach and Results: In preliminary safety analyses, high intranasal doses (up to 1010 50% tissue culture infectious dose [TCID50]) of MORV were not associated with significant adverse effects in immune competent, non–tumor-bearing mice. MORV was shown to be efficacious in a Hep3B hepatocellular cancer xenograft model but not in a CCA xenograft HuCCT1 model. In an immune competent, syngeneic murine CCA model, single intratumoral treatments with MORV (1 × 107 TCID50) triggered a robust antitumor immune response leading to substantial tumor regression and disease control at a dose 10-fold lower than VSV (1 × 108 TCID50). MORV led to increased CD8+ cytotoxic T cells without compensatory increases in tumor-associated macrophages and granulocytic or monocytic myeloid-derived suppressor cells. Conclusions: Our findings indicate that wild-type MORV is safe and can induce potent tumor regression via immune-mediated and immune-independent mechanisms in HCC and CCA animal models without dose limiting adverse events. These data warrant further development and clinical translation of MORV as an oncolytic virotherapy platform.",
author = "Nagalo, {Bolni Marius} and Yumei Zhou and Loeuillard, {Emilien J.} and Chelsae Dumbauld and Oumar Barro and Elliott, {Natalie M.} and Baker, {Alexander T.} and Mansi Arora and Bogenberger, {James M.} and Nathalie Meurice and Joachim Petit and Uson, {Pedro Luiz Serrano} and Faaiq Aslam and Elizabeth Raupach and Musa Gabere and Alexei Basnakian and Simoes, {Camila C.} and Cannon, {Martin J.} and Post, {Steven R.} and Kenneth Buetow and Chamcheu, {Jean Christopher} and Barrett, {Michael T.} and Duda, {Dan G.} and Bertram Jacobs and Richard Vile and Barry, {Michael A.} and Roberts, {Lewis R.} and Sumera Ilyas and Borad, {Mitesh J.}",
note = "Funding Information: Dan G. Duda advises Innocoll. He received grants from Bayer, Exelixis, Surface Oncology, and BMS. Lewis R. Roberts advises and has received grants from Bayer and Gilead. He consults for AstraZeneca, Global Life Science, MJH Life Sciences, Novartis Venture Fund, Pontifax, and Roche. He advises Eisai, Exact Sciences, Genentech, GRAIL, Hepion, and The Lynx Group. He has received grants from Boston Scientific, Exact Sciences, Fujifilm, Glycotest, RedHill, and TARGET PharmaSolutions. Mitesh J. Borad consults for ADC Therapeutics, Exelixis, Inspyr, G1 Therapeutics, Immunovative, OncBioMune, Western Oncolytics, and Lynx. He has received grants from, AstraZeneca, Senhwa Pharmaceuticals, Adaptimmune, Halozyme, Celgene, Five Prime, EMD Merck Serono, Taiho, Sun Biopharmaceuticals, Boston Biomed, Basilea, Toray, Dicerna, Isis Pharmaceuticals, Incyte, Mirna, Medimmune, Bioline, Sillhajen, ARIAD, PUMA, Novartis, QED, and Pieris. He is an inventor in a patent filed by Mayo Clinic. Sumera Ilyas consults for AstraZeneca. Funding Information: This study used a panel of nine human CCA cell lines (HuCCT‐1, EGI‐1, CAK‐1, SNU‐245, SNU‐308, SNU‐869, SNU‐1070, RBE, GBD‐1), one carcinoma of the ampulla of Vater, a transformed cholangiocyte cell line (H69), a murine CCA (SB), 4 human HCC cell lines (HepG2, Hep3B, Huh7, Sk‐Hep‐1), and three murine HCC cell lines (R1LWT, R2LWT, HCA‐1). All cell lines were cultured at 37°C with 5% carbon dioxide in media supplemented with L‐glutamine and antibiotic agent (100 μg ml penicillin and 100 μg ml streptomycin). EGI‐1, CAK‐1, SNU‐245, SNU‐308, SNU‐869, SNU‐1070, RBE, and GBD‐1 were maintained in RPMI 1640 medium with 10% fetal bovine serum (FBS). PAX‐42, HuCCT‐1, H69, BHK‐21 (Baby Hamster kidney fibroblast), A549 (human lung tumor cells), and Vero (African green monkey kidney) cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM) with 10% FBS. CAK‐1, GBD‐1, and H69 were gifts from Dr. Gregory Gores at Mayo Clinic. A patient‐derived cell line (PAX‐42, grown in DMEM with 10% FBS and 100 μg ml Primocin, Invivogen, San Diego, CA, USA) was a gift from Dr. Mark Truty at Mayo Clinic. HAP1 parental cell line and LDLR KO cell line were obtained from Horizon and maintained in Iscove's Modified Dulbecco's Medium supplemented with 10% FBS, 1% antibiotic. We obtained the HuCCT‐1 cell line from the Japanese Collection of Research Bioresources. EGI‐1 was purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ). SNU‐245, SNU‐308, SNU‐869, and SNU‐1079 were obtained from the Korean Cell Line Bank. RBE was purchased from the National Bio‐Resource Project of the Ministry of Education, Culture Sports, Science and Technology (RIKEN). BHK‐21, A549, and Vero cells were obtained from the American Type Culture Collection. Hep3B, HepG2, Huh7, Sk‐Hep1, and Hepa 1–6 were purchased from the American Type Culture Collection (ATCC) and were grown in DMEM with 10% FBS and in RPMI with 10% FBS, respectively. The two clones derived from the RIL‐175 cell line (R1LWT, R2LWT), HCA‐1 and SB cells, were grown in DMEM with 10% FBS. −1 −1 −1 Funding Information: This research was funded by National Institute of Health (NIH) through a DP2 award CA195764 (to M.J.B.); by National Cancer Institute K12 award CA090628 (to M.J.B.); by a P50 grant CA210964 (to M.J.B., R.V., and L.R.R.) and a K01 award CA234324 (to B.M.N.); and by start‐up funds from the Winthrop P. Rockefeller Cancer Institute–University of Arkansas for Medical Sciences (to B.M.N.). The research of D.G.D. is supported by NIH grants R01CA260872, R01CA260857, R01CA247441, and R03CA256764 and by Department of Defense peer review cancer research program (PRCRP) grants #W81XWH‐19‐1‐0284 and W81XWH‐21‐1‐0738. C.D. received a small grant from the Department of Molecular Medicine at Mayo Clinic. M.J.B. has received a grant to 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 from ADC Therapeutics, Exelixis Pharmaceuticals, Inspyr Therapeutics, G1 Therapeutics, Immunovative Therapies, OncBioMune Pharmaceuticals, Western Oncolytics, and Lynx Group; and travel support from Astra Zeneca. D.G.D. received consultant fees from Bayer, BMS, Simcere, Sophia Biosciences, and Surface Oncology and has received research grants from Bayer, Merrimack, Exelixis, and BMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2022 American Association for the Study of Liver Diseases.",
year = "2022",
doi = "10.1002/hep.32769",
language = "English (US)",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
}