Oncolytic virus VT1092M synergizes with immune checkpoint inhibitors against intraperitoneal metastases of colorectal cancer
- 1School of Pharmacy, Yantai University , , ,
- 2Beijing WellGene Company, Ltd , ,
Abstract
Background: Intraperitoneal metastasis is a frequent progression in colon cancer, highlighting the critical need for enhanced therapeutic approaches. Oncolytic virus (OV) therapy has emerged as a promising immunotherapeutic strategy. The combination of OVs with immune checkpoint inhibitors (ICIs) has demonstrated an enhanced anti-tumor response.
Methods: We generated the intraperitoneal-subcutaneous bilateral colon cancer xenograft model to simulate intraperitoneal metastatic colon cancer, and evaluated the systemic antitumor efficacy of the oncolytic HSV-1 virus VT1092M in combination with ICIs (anti-PD-L1 antibody and anti-CTLA-4 antibody).
Results and discussion: Intraperitoneal administration of VT1092M markedly suppressed intraperitoneal cancer progression and enhanced the superior antitumor efficacy of ICIs immunotherapy in murine intraperitoneal metastatic colon cancer. Notably, treatment of VT1092M combined with anti-CTLA-4 antibody could eliminate both intraperitoneal metastases and subcutaneous tumors, while also inhibiting the formation of peritoneal blood vessels and malignant ascites. The synergistic combination of VT1092M and anti-CTLA-4 elicited potent intraperitoneal and systemic antitumor immunity, culminating in durable, tumor-specific memory that significantly prolonged survival in mice with colorectal intraperitoneal metastases compared to either monotherapy. Mechanistically, the combination therapy activates the anti-tumor immune environment within the peritoneal cavity, leading to a significant increase in tumoricidal CD8 ⁺ T cells and M1 macrophages, as well as the reprogramming of transcriptional signatures associated with the tumor immune response within the tumor microenvironment. Ultimately, intraperitoneal immunotherapy with VT1092M enhances the efficacy of immune checkpoint blockade in suppressing intraperitoneal metastatic colorectal cancer and induces durable tumor-specific immune memory, thereby exerting substantial anti-tumor effects. This finding highlights the potential of synergistically combining oncolytic viruses with ICIs to advance immunotherapeutic strategies for intraperitoneal metastatic colorectal cancer.
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BibTeX
@article{hu2026oncolytic,
title = {{Oncolytic virus VT1092M synergizes with immune checkpoint inhibitors against intraperitoneal metastases of colorectal cancer}},
author = {Zongfeng Hu and Xinru Yuan and Shuzhen Li and Wenqi Liu and Jiajia Liu and Hua Zhou and Chunyang Sun and Chao Tian and Kaixuan Xue and Yiting Cheng and Jinyu Wang and Haitian Xu and Jianshuai Yang and Xiaopeng Li and Jingfeng Li},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1926207},
url = {https://europepmc.org/article/PMC/PMC13662124},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oncolytic virus VT1092M synergizes with immune checkpoint inhibitors against intraperitoneal metastases of colorectal cancer
AU - Zongfeng Hu
AU - Xinru Yuan
AU - Shuzhen Li
AU - Wenqi Liu
AU - Jiajia Liu
AU - Hua Zhou
AU - Chunyang Sun
AU - Chao Tian
AU - Kaixuan Xue
AU - Yiting Cheng
AU - Jinyu Wang
AU - Haitian Xu
AU - Jianshuai Yang
AU - Xiaopeng Li
AU - Jingfeng Li
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1926207
UR - https://europepmc.org/article/PMC/PMC13662124
AB - Background: Intraperitoneal metastasis is a frequent progression in colon cancer, highlighting the critical need for enhanced therapeutic approaches. Oncolytic virus (OV) therapy has emerged as a promising immunotherapeutic strategy. The combination of OVs with immune checkpoint inhibitors (ICIs) has demonstrated an enhanced anti-tumor response. Methods: We generated the intraperitoneal-subcutaneous bilateral colon cancer xenograft model to simulate intraperitoneal metastatic colon cancer, and evaluated the systemic antitumor efficacy of the oncolytic HSV-1 virus VT1092M in combination with ICIs (anti-PD-L1 antibody and anti-CTLA-4 antibody). Results and discussion: Intraperitoneal administration of VT1092M markedly suppressed intraperitoneal cancer progression and enhanced the superior antitumor efficacy of ICIs immunotherapy in murine intraperitoneal metastatic colon cancer. Notably, treatment of VT1092M combined with anti-CTLA-4 antibody could eliminate both intraperitoneal metastases and subcutaneous tumors, while also inhibiting the formation of peritoneal blood vessels and malignant ascites. The synergistic combination of VT1092M and anti-CTLA-4 elicited potent intraperitoneal and systemic antitumor immunity, culminating in durable, tumor-specific memory that significantly prolonged survival in mice with colorectal intraperitoneal metastases compared to either monotherapy. Mechanistically, the combination therapy activates the anti-tumor immune environment within the peritoneal cavity, leading to a significant increase in tumoricidal CD8 ⁺ T cells and M1 macrophages, as well as the reprogramming of transcriptional signatures associated with the tumor immune response within the tumor microenvironment. Ultimately, intraperitoneal immunotherapy with VT1092M enhances the efficacy of immune checkpoint blockade in suppressing intraperitoneal metastatic colorectal cancer and induces durable tumor-specific immune memory, thereby exerting substantial anti-tumor effects. This finding highlights the potential of synergistically combining oncolytic viruses with ICIs to advance immunotherapeutic strategies for intraperitoneal metastatic colorectal cancer.
SN - 1664-3224
ER -