Intraperitoneal Administration of MRNA Encoding Interleukin-12 for Immunotherapy in Peritoneal Carcinomatosis

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2025 Feb 18

PMID 39962479

Authors

Leire Arrizabalaga

Claudia Augusta Di Trani

Myriam Fernandez-Sendin

Angela Bella

Joan Salvador Russo-Cabrera

Celia Gomar

Nuria Ardaiz

Virginia Belsue

Jose Gonzalez-Gomariz

Sara Zalba

Adrian Gil-Korilis

Maria J Garrido

Ignacio Melero

Fernando Aranda

Pedro Berraondo

Affiliations

Soon will be listed here.

Abstract

Peritoneal carcinomatosis is an advanced stage of cancer with very limited treatment options. Locoregional immunotherapy is being evaluated as a way to improve efficacy and limit toxicity. This study assessed the efficacy of a cationic polymer/lipid-based transfection compound in delivering mRNA molecules intraperitoneally. Our investigation of the transfer of luciferase mRNA in murine models of peritoneal carcinomatosis revealed preferential luciferase expression in the omentum upon the intraperitoneal administration of complexed mRNAs. Macrophages were identified as key cells that capture and express the mRNA complexes, and accordingly, depletion of resident macrophages led to reduced reporter luciferase expression. To explore the therapeutic potential of this approach, mRNA complexes encoding single-chain interleukin-12 (IL12), an immunostimulatory molecule (mRNA-IL12), were investigated. mRNA-IL12-treated mice exhibited a significant survival advantage in models of peritoneal carcinomatosis and acquired immune memory, as shown upon subcutaneous rechallenge. Tumor microenvironment analyses revealed increased numbers of CD4 and CD8 T cells with a more proliferative phenotype, accompanied by decreased myeloid populations in the omentum. Overall, our study underscores the potential of mRNA complexes for efficient mRNA delivery, eliciting effective antitumor responses and modulating the tumor microenvironment to treat peritoneal carcinomatosis.

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