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Abstract The members of the vesiculovirus genus have recently become attractive immunotherapeutic agents due to their natural selectivity for tumors and lack of toxicity in humans. Here, the research shows Intratumoral (IT) or Intraperitoneal (IP) injection of JURV was found to induce dynamic tumor regression in human hepatocellular carcinoma (HCC) xenografts and syngeneic models. Furthermore, IT injections of JURV were also shown to recruit and activate cytotoxic T lymphocytes and decrease tumor-associated macrophage infiltration, resulting in the delay of tumor growth in both local and distant murine HCC tumors established in a syngeneic model. Additionally, the concurrent use of JURV and anti-PD-1 antibodies was found to synergistically modulate the tumor microenvironment (TME) via increased tumor-infiltrating CD4+ T cells and depleted CD8+ PD-1+ and NK cells. Furthermore, using RIL-175, an aggressive metastatic HCC tumor mouse model, we show that intraperitoneal (IP) (systemic) administration of JURV and anti-PD1 significantly improved long-term survival (90%) compared to the (20%) JURV or anti-PD1 alone. Through proteogenomic analysis, the activation of different effectors of the immune system was observed to cooperate to alter the TME to a favorable anti-tumor immune state. These findings further support the development of JURV as an immunovirotherapy platform for HCC, with the potential to induce abscopal effects via the activation of several tumor suppressor genes and the mechanism regulating the T helper cell responses. Citation Format: Mulu Z. Tesfay, Khandoker U. Ferdous, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Steven R. Post, Thomas J. Kelly, Martin J. Cannon, Alexei Basnakian, Bolni M. Nagalo. Oncolytic Jurona-driven systemic and intratumoral immunotherapy combined with immune checkpoint blockade boost immune response and survival in hepatocellular carcinoma models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5004.
Tesfay et al. (Fri,) studied this question.