Enhancing immune response and survival in hepatocellular carcinoma with novel oncolytic Jurona virus and immune checkpoint blockade
Members of the <i>Vesiculovirus</i> genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by coordinated activation of immune effectors, which modulate the tumor microenvironment into a state conducive to anti-tumor activity. Our results establish JURV as a potent candidate for immunovirotherapy in HCC, capable of modulating immune response and synergizing with standard of care for HCC to prolong survival in preclinical models. Further, this research deepens our understanding of JURV's anti-tumoral mechanisms and highlights its potential as a novel approach to HCC treatment strategies.
Authors
- Bahaa Mustafa (ORCID: https://orcid.org/0000-0002-3306-6140)
- Aleksandra Cios
- Alicia L. Graham
- Natalie M. Elliott (ORCID: https://orcid.org/0000-0002-4130-1286)
- Mitesh J. Borad (ORCID: https://orcid.org/0000-0003-2700-2658)
- Mika Taylor
- Dan G. Duda (ORCID: https://orcid.org/0000-0001-7065-8797)
- Khandoker Usran Ferdous
- Steven R. Post (ORCID: https://orcid.org/0000-0002-4711-1723)
- Chelsae R Watters (ORCID: https://orcid.org/0000-0001-6916-6509)
- Lewis R. Roberts (ORCID: https://orcid.org/0000-0001-7885-8574)
- Emmanouil Giorgakis (ORCID: https://orcid.org/0000-0002-5019-5497)
- Martin J. Cannon (ORCID: https://orcid.org/0000-0003-2656-187X)
- Mulu Z. Tesfay
- Omeed Moaven (ORCID: https://orcid.org/0000-0002-0560-0457)
- Chiswili Chabu (ORCID: https://orcid.org/0000-0001-9585-5527)
- Yuguo Zhang (ORCID: https://orcid.org/0000-0001-7220-2814)
- Stephanie D. Byrum (ORCID: https://orcid.org/0000-0002-1783-3610)
- Duah Alkam (ORCID: https://orcid.org/0000-0002-5965-7694)
- Thomas Kelly (ORCID: https://orcid.org/0000-0001-6285-1925)
- Jean Christopher Chamcheu (ORCID: https://orcid.org/0000-0002-3927-5664)
- Martín E. Fernández-Zapico (ORCID: https://orcid.org/0000-0002-8089-3907)
- Oumar Barro
- Randal S. Shelton
- Allen Gies (ORCID: https://orcid.org/0000-0003-2492-0429)
- Camila Simões (ORCID: https://orcid.org/0000-0001-9828-6112)
- Charity L. Washam (ORCID: https://orcid.org/0000-0001-5761-9304)
- Rang Govindarajan
- Bolni Marius Nagalo (ORCID: https://orcid.org/0000-0002-2173-7912)
- Alexei G. Basnakian (ORCID: https://orcid.org/0000-0002-9115-6283)
- Jun Ying (ORCID: https://orcid.org/0009-0006-5684-794X)
Institutions
- Mayo Clinic (US)
- Washington University in St. Louis (US)
- Massachusetts General Hospital (US)
- Novel (United States) (US)
- Mayo Clinic in Arizona (US)
- Winthrop Rockefeller Foundation (US)
- Louisiana Cancer Research Center (US)
- Arkansas Department of Health (US)
- University of Louisiana at Monroe (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- University of Missouri (US)
- University of Arkansas for Medical Sciences (US)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1016/j.omton.2024.200913
- Citations
- 4
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 2.20
Funders
- American Association for Cancer Research
- University of Arkansas for Medical Sciences
- National Institutes of Health
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences
- NIH Office of the Director
- National Cancer Institute
- National Institute of General Medical Sciences