Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers

Bolni Marius Nagalo^{1

2

3}, Yumei Zhou^{1

4}, Emilien J Loeuillard⁵, Chelsae Dumbauld^{1

4}, Oumar Barro^{1

4}, Natalie M Elliott^{1

4}, Alexander T Baker^{1

4}, Mansi Arora^{1

4}, James M Bogenberger^{1

4}, Nathalie Meurice^{1

4}, Joachim Petit^{1

4}, Pedro Luiz Serrano Uson Jr^{1

4

6}, Faaiq Aslam^{1

4}, Elizabeth Raupach^{1

4}, Musa Gabere^{1

4}, Alexei Basnakian^{2

7}, Camila C Simoes^{2

3}, Martin J Cannon^{3

8}, Steven R Post^{2

3}, Kenneth Buetow⁹, Jean Christopher Chamcheu¹⁰, Michael T Barrett^{1

4}, Dan G Duda¹¹, Bertram Jacobs¹², Richard Vile^{1

13}, Michael A Barry^{1

13

14}, Lewis R Roberts⁵, Sumera Ilyas⁵, Mitesh J Borad^{1

4

13

15}

Affiliations

¹ Department of Molecular Medicine , Mayo Clinic , Rochester , Minnesota , USA.
² Department of Pathology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
³ The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁴ Division of Hematology and Medical Oncology , Mayo Clinic , Phoenix , Arizona , USA.
⁵ Division of Gastroenterology and Hepatology , Mayo Clinic , Rochester , Minnesota , USA.
⁶ Center for Personalized Medicine , Hospital Israelita Albert Einstein , São Paulo , Brazil.
⁷ Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁸ Department of Microbiology and Immunology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁹ Computational Sciences and Informatics Program for Complex Adaptive System Arizona State University , Tempe , Arizona , USA.
¹⁰ School of Basic Pharmaceutical and Toxicological Sciences , College of Pharmacy, University of Louisiana , Monroe , Louisiana , USA.
¹¹ Steele Laboratories for Tumor Biology, Department of Radiation Oncology , Massachusetts General Hospital and Harvard Medical School , Boston , Massachusetts , USA.
¹² Center for Infectious Diseases and Vaccinology , the Biodesign Institute, Arizona State University , Tempe , Arizona , USA.
¹³ Mayo Clinic Comprehensive Cancer Center , Phoenix , Minnesota , USA.
¹⁴ Division of Infectious Diseases, Department of Internal Medicine , Mayo Clinic Rochester , Rochester , Minnesota , USA.
¹⁵ Mayo Clinic Center for Individualized Medicine , Rochester , Minnesota , USA.

PMID: 36052732
DOI: 10.1002/hep.32769

Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers

Bolni Marius Nagalo et al. Hepatology. 2023.

. 2023 Jun 1;77(6):1943-1957.

doi: 10.1002/hep.32769. Epub 2022 Oct 11.

Authors

Affiliations

¹ Department of Molecular Medicine , Mayo Clinic , Rochester , Minnesota , USA.
² Department of Pathology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
³ The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁴ Division of Hematology and Medical Oncology , Mayo Clinic , Phoenix , Arizona , USA.
⁵ Division of Gastroenterology and Hepatology , Mayo Clinic , Rochester , Minnesota , USA.
⁶ Center for Personalized Medicine , Hospital Israelita Albert Einstein , São Paulo , Brazil.
⁷ Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁸ Department of Microbiology and Immunology , University of Arkansas for Medical Sciences , Little Rock , Arkansas , USA.
⁹ Computational Sciences and Informatics Program for Complex Adaptive System Arizona State University , Tempe , Arizona , USA.
¹⁰ School of Basic Pharmaceutical and Toxicological Sciences , College of Pharmacy, University of Louisiana , Monroe , Louisiana , USA.
¹¹ Steele Laboratories for Tumor Biology, Department of Radiation Oncology , Massachusetts General Hospital and Harvard Medical School , Boston , Massachusetts , USA.
¹² Center for Infectious Diseases and Vaccinology , the Biodesign Institute, Arizona State University , Tempe , Arizona , USA.
¹³ Mayo Clinic Comprehensive Cancer Center , Phoenix , Minnesota , USA.
¹⁴ Division of Infectious Diseases, Department of Internal Medicine , Mayo Clinic Rochester , Rochester , Minnesota , USA.
¹⁵ Mayo Clinic Center for Individualized Medicine , Rochester , Minnesota , USA.

PMID: 36052732
DOI: 10.1002/hep.32769

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 10 10 50% tissue culture infectious dose [TCID 50 ]) 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 × 10 7 TCID 50 ) triggered a robust antitumor immune response leading to substantial tumor regression and disease control at a dose 10-fold lower than VSV (1 × 10 8 TCID 50 ). 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.

Trial registration: ClinicalTrials.gov NCT01628640.

PubMed Disclaimer

References

1. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6.
1. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905.
1. Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J Clin Oncol. 2021;39(27):2991–3001.
1. Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557–88.
1. Lawler SE, Speranza MC, Cho CF, Chiocca EA. Oncolytic viruses in cancer treatment: a review. JAMA Oncol. 2017;3:841–9.

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers

Affiliations

Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical