Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy

In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings...

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Main Authors: Chunqing Gao, Qi Ying, Yufeng Qiu, Ningbo Ren, Kan Chen, Yanrong Zhou, Ting Ye, Gongchu Li
Format: Article
Language:English
Published: Elsevier 2024-09-01
Series:Molecular Therapy: Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950329924000651
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author Chunqing Gao
Qi Ying
Yufeng Qiu
Ningbo Ren
Kan Chen
Yanrong Zhou
Ting Ye
Gongchu Li
author_facet Chunqing Gao
Qi Ying
Yufeng Qiu
Ningbo Ren
Kan Chen
Yanrong Zhou
Ting Ye
Gongchu Li
author_sort Chunqing Gao
collection DOAJ
description In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings reveal that oncoVV-CLEC2A effectively suppresses colorectal proliferation of mouse xenografts and a range of human cancer cell lines by augmenting viral reproduction capabilities, including the lung cancer H460 cell line, colorectal cancer cell lines (HCT116 and SW620), and hepatocellular carcinoma HuH-7 cell line. Moreover, it is evident that oncoVV-CLEC2A can induce antitumor immunity by boosting cytokine production but not antivirus response, and enhancing calreticulin expression. Further investigation indicates that oncoVV-CLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-γ and induce M1-like macrophage polarization. These findings shed light on the antitumor mechanisms of oncoVV-CLEC2A, provide a theoretical basis for oncolytic therapies, and lay the groundwork for novel strategies for modifying VVs.
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series Molecular Therapy: Oncology
spelling doaj-art-4046597af92747dbafb8310fc3d7cae02025-08-20T02:22:32ZengElsevierMolecular Therapy: Oncology2950-32992024-09-0132320082310.1016/j.omton.2024.200823Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacyChunqing Gao0Qi Ying1Yufeng Qiu2Ningbo Ren3Kan Chen4Yanrong Zhou5Ting Ye6Gongchu Li7College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaCollege of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China; Corresponding author: Ting Ye, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China; Corresponding author: Gongchu Li, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings reveal that oncoVV-CLEC2A effectively suppresses colorectal proliferation of mouse xenografts and a range of human cancer cell lines by augmenting viral reproduction capabilities, including the lung cancer H460 cell line, colorectal cancer cell lines (HCT116 and SW620), and hepatocellular carcinoma HuH-7 cell line. Moreover, it is evident that oncoVV-CLEC2A can induce antitumor immunity by boosting cytokine production but not antivirus response, and enhancing calreticulin expression. Further investigation indicates that oncoVV-CLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-γ and induce M1-like macrophage polarization. These findings shed light on the antitumor mechanisms of oncoVV-CLEC2A, provide a theoretical basis for oncolytic therapies, and lay the groundwork for novel strategies for modifying VVs.http://www.sciencedirect.com/science/article/pii/S2950329924000651MT: Regular IssueC-type lectin domain family 2 member Aoncolytic vaccinia virusantitumorviral replicationNK cells
spellingShingle Chunqing Gao
Qi Ying
Yufeng Qiu
Ningbo Ren
Kan Chen
Yanrong Zhou
Ting Ye
Gongchu Li
Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
Molecular Therapy: Oncology
MT: Regular Issue
C-type lectin domain family 2 member A
oncolytic vaccinia virus
antitumor
viral replication
NK cells
title Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
title_full Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
title_fullStr Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
title_full_unstemmed Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
title_short Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy
title_sort oncolytic vaccinia virus harboring clec2a gene enhances viral replication and antitumor efficacy
topic MT: Regular Issue
C-type lectin domain family 2 member A
oncolytic vaccinia virus
antitumor
viral replication
NK cells
url http://www.sciencedirect.com/science/article/pii/S2950329924000651
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