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

Gomar C., Risson A., Arrizabalaga L., Ardaiz N., Belsue V., Gil-Korilis A., Ahmadi-Erber S., Schippers T., Melero I., Orlinger KK., Aranda F., Lauterbach H., Berraondo P.

Peritoneal carcinomatosis remains a challenging clinical condition with limited therapeutic options. 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. Intraperitoneal administration of artLCMV-NanoLuc resulted in sustained, high-level transgene expression in the peritoneal cavity for over 40 days. The antitumor efficacy of artLCMV.gp70 was significantly enhanced by IL12, eliciting a robust immune response in the MC38 model. In contrast, artLCMV.gp70 and artLCMV.FRα effectively reduced tumor burden and prolonged survival in ID8-VEGF mice, but coexpression of IL12 or 4-1BBL did not provide additional therapeutic benefit. These findings demonstrate that recombinant artLCMV vectors offer a promising therapeutic strategy for peritoneal carcinomatosis, delivering long-lasting transgene expression and potent antitumor effects. The addition of immunostimulatory molecules such as IL12 may enhance efficacy in certain tumor models, though its effects appear to be context-dependent.

DOI

10.1080/2162402x.2025.2520266

Type

Journal article

Journal

Oncoimmunology

Publication Date

12/2025

Volume

14

Addresses

Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain.

Keywords

Cell Line, Tumor, Animals, Humans, Mice, Peritoneal Neoplasms, Ovarian Neoplasms, Disease Models, Animal, Interleukin-12, Injections, Intraperitoneal, Xenograft Model Antitumor Assays, Genetic Vectors, Female, Folate Receptor 1

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