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Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer.

Authors
  • Lee, Yu Seong1
  • Lee, Won Suk2
  • Kim, Chang Woo3
  • Lee, Seung Joon1
  • Yang, Hannah2
  • Kong, So Jung2
  • Ning, John4
  • Yang, Kyung-Mee5
  • Kang, Beodeul2
  • Kim, Woo Ram2
  • Chon, Hong Jae6
  • Kim, Chan6
  • 1 Department of Biomedical Science, CHA University, Seongnam, Korea (the Republic of). , (North Korea)
  • 2 Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea (the Republic of). , (North Korea)
  • 3 Kyung Hee University Gangdong Hospital, Gangdong-gu, Korea (the Republic of). , (North Korea)
  • 4 SillaJen Biotherapeutics, San Francisco, California, USA.
  • 5 SillaJen, Busan, Korea (the Republic of). , (North Korea)
  • 6 Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea (the Republic of) [email protected] [email protected] , (North Korea)
Type
Published Article
Journal
Journal for ImmunoTherapy of Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 01, 2020
Volume
8
Issue
2
Identifiers
DOI: 10.1136/jitc-2020-000857
PMID: 33199510
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Peritoneal carcinomatosis (PC) is a common and devastating manifestation of colon cancer and refractory to conventional anticancer therapeutics. During the peritoneal dissemination of colon cancer, peritoneal immunity is nullified by various mechanisms of immune evasion. Here, we employed the armed oncolytic vaccinia virus mJX-594 (JX) to rejuvenate the peritoneal antitumor immune responses in the treatment of PC. PC model of MC38 colon cancer was generated and intraperitoneally treated with JX and/or anti-programmed cell death protein 1 (PD-1) antibody. The peritoneal tumor burden, vascular leakage, and malignant ascites formation were then assessed. Tumors and peritoneal lavage cells were analyzed by flow cytometry, multiplex tissue imaging, and a NanoString assay. JX treatment effectively suppressed peritoneal cancer progression and malignant ascites formation. It also restored the peritoneal anticancer immunity by activating peritoneal dendritic cells (DCs) and CD8+ T cells. Moreover, JX selectively infected and killed peritoneal colon cancer cells and promoted the intratumoral infiltration of DCs and CD8+ T cells into peritoneal tumor nodules. JX reinvigorates anticancer immunity by reprogramming immune-related transcriptional signatures within the tumor microenvironment. Notably, JX cooperates with immune checkpoint inhibitors (ICIs), anti-programmed death-1, anti-programmed death-ligand 1, and anti-lymphocyte-activation gene-3 to elicit a stronger anticancer immunity that eliminates peritoneal metastases and malignant ascites of colon cancer compared with JX or ICI alone. Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

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