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posted on 2023-04-03, 23:12 authored by Almohanad A. Alkayyal, Lee-Hwa Tai, Michael A. Kennedy, Christiano Tanese de Souza, Jiqing Zhang, Charles Lefebvre, Shalini Sahi, Abhirami A. Ananth, Ahmad Bakur Mahmoud, Andrew P. Makrigiannis, Greg O. Cron, Blair Macdonald, E. Celia Marginean, David F. Stojdl, John C. Bell, Rebecca C. Auer Supplementary figure S.2: Viral fitness, kinetics and tumour cytotoxicity.
Funding
Terry Fox Research Institute
Canadian Cancer Society Research Institute
Canadian Institute of Health Research
University of Tabuk
Canadian Institutes of Health Research
Ontario Ministry of Research and Development Early Researcher Award
History
ARTICLE ABSTRACT
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.
