Locoregional modified vaccinia ankara (MVA) encoding a single-chain IL-12 achieves efficacy antitumor immune response in peritoneal carcinomatosis

Abstract Peritoneal carcinomatosis is an advanced stage of cancer developed in the peritoneal cavity without effective treatment. In order to restore antitumor immunity subverted by tumor cells, we evaluated in this study intraperitoneal administration of vaccinia virus Ankara (MVA) genetically modified to express the proinflammatory cytokine single-chain interleukin 12. MVA encoding scIL-12 was evaluated in peritoneal carcinomatosis models based on intraperitoneal administration of tumor cells. The immune response was evaluated by ELISpot, flow cytometry, intravital microscopy, and depleting monoclonal antibodies. Safety was assessed by measuring body weight and a hemogram test. Tissue tropism after intravenous or intraperitoneal administration was determined by bioluminescence analysis after the administration of MVA encoding luciferase. Intraperitoneal or locoregional administration, but not other routes of administration, elicited a potent immune response characterized by increased levels of tumor-specific T CD8 lymphocytes. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result, a single intraperitoneal administration of MVA encoding scIL-12 completely eradicates MC38 cells implanted in the peritoneum, protecting cured mice from a subcutaneous rechallenge with MC38 cells. The safety profile of intraperitoneal administration was also superior to that of intravenous administration since there was no weight loss or hematological toxicity when the vector was infused into the peritoneal cavity. In conclusion, intraperitoneal administration of MVA vectors encoding scIL-12 induces a potent tumor-specific immune response that leads to the eradication of peritoneal metastasis. Citation Format: Ángela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, José González-Gomariz, Assunta Cirella, Irene Olivera, Maite Alvarez, Álvaro Teijeira, Cigdem Atay Langbein, José Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda. Locoregional modified vaccinia ankara (MVA) encoding a single-chain IL-12 achieves efficacy antitumor immune response in peritoneal carcinomatosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2736.