Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with dismal prognosis. Oncolytic virotherapy is a promising anticancer treatment that directly lyses tumor cells. Coxsackievirus A11 (CVA11) is an emerging oncolytic virus against solid cancers. Herein we tested whether CVA11 infection has an oncolytic activity in human MPM cell lines and identified its cognate receptor. We found that CVA11 infection shows a remarkable oncolytic activity in six of six human MPM cell lines. MPM cells having higher intercellular adhesion molecule-1 (ICAM-1) expression showed higher CVA11-induced cytotoxicity, and that identified ICAM-1 as its surface receptor because coinfection with neutralizing ICAM-1 antibody substantially abrogated CVA11-triggered cytotoxicity in MPM cells. In addition, we unraveled that the activations of both phosphoinositide 3-kinase/Akt and mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) signaling pathways partially but significantly contributed to the CVA11-triggered cytotoxicity of CVA11 as evidenced by treating with respective inhibitors. Taken together, our findings show a novel oncolytic virotherapy using CVA11 could be an alternative therapeutic modality for human MPM.

Citation Format: Koji Okamura, Hiroyuki Inoue, Yuki Ikematsu, Rie Furukawa, Keiichi Ota, Yasuto Yoneshima, Eiji Iwama, Kentaro Tanaka, Isamu Okamoto. Coxsackievirus A11 elicits a potent oncolytic activity in human malignant pleural mesothelioma via ICAM-1 receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1918.