한빛사논문
- 조회860
Yu Seong Lee1,†, Won Suk Lee2,†, Chang Woo Kim3,†, Seung Joon Lee1, Hannah Yang2, So Jung Kong2, John Ning4, Kyung-Mee Yang5, Beodeul Kang2, Woo Ram Kim2, Hong Jae Chon2,* and Chan Kim2,*
1Department of Biomedical Science, CHA University, Seongnam, Korea (the Republic of)
2Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea (the Republic of)
3Kyung Hee University Gangdong Hospital, Gangdong-gu, Korea (the Republic of)
4SillaJen Biotherapeutics, San Francisco, California, USA
5SillaJen, Busan, Korea (the Republic of)
†YSL, WSL and CWK contributed equally.
*Correspondence to Dr Chan Kim, Dr Hong Jae Chon
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.
논문정보
- Research article
- 2020년 11월 (BRIC 등록일 2020-11-30)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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