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848 The long-lasting expression of recombinant artLCMV following intraperitoneal administration exerts potent antitumor effects on tumor models of peritoneal carcinomatosis

jitc · 2025-11-04 · canonical JSON source

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Background Peritoneal carcinomatosis (PC) is a challenging condition with limited therapeutic options. It occurs when a primary tumor in the peritoneal cavity progresses to a metastatic stage. Viral vectors based on lymphocytic choriomeningitis virus (artLCMV) may be a potential strategy against PC by inducing a robust and long-lasting T-cell response.Methods In this study, we evaluated the efficacy of a recombinant artLCMV platform encoding tumor antigens and immune-stimulatory molecules in preclinical models. We analyzed the expression kinetics, biodistribution, and antitumor activity of artLCMV vectors encoding the reporter protein NanoLuc, tumor-associated antigens such as gp70 or folate receptor alpha (FRα), and immune-stimulatory molecules including IL12 or 4-1BBL. These vectors were tested in murine models of peritoneal carcinomatosis established by intraperitoneal inoculation of MC38 colon cancer cells or ID8-VEGF ovarian cancer cells.Results Our results showed that the intraperitoneal administration of artLCMV-NanoLuc achieved sustained transgene expression in the peritoneal cavity for over 40 days ( figure 1a). Biodistribution analysis revealed that while bioluminescence was observed in all analyzed tissues, the highest signal intensity was found in peritoneal-associated tissues, including the mesentery and omentum (figure 1b). The antitumor efficacy of artLCMV.gp70 was enhanced by the coexpression of IL12, eliciting a strong immune response in the MC38 model (figure 2a-b). Conversely, while artLCMV.gp70 and artLCMV.FRα showed potent antitumor efficacy and extended survival in ID8-VEGF-treated mice, adding IL12 or 4-1BBL did not further improve therapeutic outcomes (figure 2c-e).Conclusions These findings highlight the potential of artLCMV as a promising therapeutic strategy for peritoneal carcinomatosis, offering durable expression and potent antitumor effects. The inclusion of immunostimulatory molecules such as IL12 may enhance efficacy in certain tumor models, but benefits are context-dependent.Abstract 848 Figure 1In vivo kinetics and biodistribution of artLCMV-NanoLuc following various routes of inoculation in tumor-bearing mice. a) in vivo kinetics of artLCMV-NanoLuc after intratumoral (i.t.), intraperitoneal (i.p.), or intravenous (i.v.) inoculation.(b) biodistribution of artLCMV-NanoLuc 24 hours after i.p. administrationAbstract 848 Figure 2Efficacy of artLCMV encoding GFP or gp70 with IL12 or 4-1BBL, and FRα with or without IL12 in the MC38 and ID8-VEGF peritoneal carcinomatosis model. A-Efficacy of artLCMV in the MC38 model. B-Immune cell profiling. C-Efficacy of artLCMV in the ID8-VEGF model. D-Efficacy of artLCMV encoding the FRα in the ID8-VEGF model. E-Efficacy of artLCMV encoding the FRα and IL12 in the ID8-VEGF model