Enhancing immune response and survival in hepatocellular carcinoma with novel oncolytic Jurona virus and immune checkpoint blockade.

Autor:	Tesfay MZ; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Zhang Y; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Ferdous KU; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Taylor MA; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Cios A; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Shelton RS; Department of Pharmacology, UAMS, Little Rock, AR, USA., Simoes CC; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Watters CR; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Barro O; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Elliott NM; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Mustafa B; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Chamcheu JC; School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, USA., Graham AL; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Washam CL; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Alkam D; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Gies A; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Byrum SD; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Giorgakis E; College of Medicine, Surgery Transplant University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA., Post SR; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Kelly T; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA., Ying J; Department of Biostatistics, UAMS College of Public Health, Little Rock, AR, USA., Moaven O; Division of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA, USA.; Department of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University (LSU) Health, New Orleans, LA, USA.; LSU-LCMC Cancer Center, New Orleans, LA, USA., Chabu CY; Division of Biological Sciences, University of Missouri, Columbia, MO, USA.; Department of Surgery, School of Medicine, University of Missouri, Columbia, MO, USA.; Siteman Cancer Center, Washington University, St. Louis, MO, USA., Fernandez-Zapico ME; Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN, USA., Duda DG; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA., Roberts LR; Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN, USA., Govindarajan R; Medical Oncology Division, Internal Medicine Department, The University of Arkansas for Medical Sciences, Little Rock, AR, USA., Borad MJ; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA., Cannon MJ; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA.; Department of Microbiology and Immunology, UAMS, Little Rock, AR, USA., Basnakian AG; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA.; Department of Pharmacology, UAMS, Little Rock, AR, USA., Nagalo BM; Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.; The Winthrop P. Rockefeller Cancer Institute, UAMS, Little Rock, AR, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Oncology [Mol Ther Oncol] 2024 Nov 26; Vol. 32 (4), pp. 200913. Date of Electronic Publication: 2024 Nov 26 (Print Publication: 2024).
DOI:	10.1016/j.omton.2024.200913
Abstrakt:	Members of the Vesiculovirus 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. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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