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

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, biodist...

Full description

Saved in:
Bibliographic Details
Main Authors: Celia Gomar, Aline Risson, Leire Arrizabalaga, Nuria Ardaiz, Virginia Belsue, Adrian Gil-Korilis, Sarah Ahmadi-Erber, Timo Schippers, Ignacio Melero, Klaus K. Orlinger, Fernando Aranda, Henning Lauterbach, Pedro Berraondo
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2520266
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2162-402X