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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing
Wen Zhang1, Xiao Hu2, Jing Liang3
1Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Abstract:
Oncolytic viruses are promising immunoreagents. Numerous studies have shown that oncolytic virotherapy is effective for many tumors. Herein, we investigated the therapeutic effect of oHSV2, an oncolytic type 2 herpes simplex virus, on mouse colon carcinoma. The in vivo antitumor efficacy of oHSV2 was observed in both unilateral and bilateral colon cancer models. oHSV2 effectively eliminated tumors and prolonged the survival of mice without side effects. Additionally, treatment with oHSV2 effectively prevented the growth of rechallenged tumors and distant implanted tumors. The specific killing ability of splenic immune cells to tumor cells was enhanced. oHSV2 treatment effectively reduced the content of inhibitory immune cells (regulatory T cells [Tregs] and myeloid-derived suppressor cells [MDSCs]) and increased the content of positive immune cells (natural killer [NK], CD8+ T, and dendritic cells [DCs]) in the spleen. Moreover, treatment with oHSV2 remodeled the tumor immune microenvironment. In summary, treatment with oHSV2 can effectively eliminate primary tumors, generate tumor-specific immunity, and elicit immune memory to inhibit tumor recurrence and metastasis. Furthermore, this virotherapy can reshape the immune status of the spleen and tumor microenvironment in mice, which can further improve the therapeutic antitumor effect.
Insights
Oncolytic herpes simplex virus type 2 (oHSV2) effectively treats mouse colon cancer by eliminating tumors and preventing recurrence. This immunotherapy enhances anti-tumor immunity and reshapes the tumor microenvironment without side effects.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Oncolytic viruses are emerging as potent immunotherapeutic agents for various cancers.
- Oncolytic virotherapy has demonstrated efficacy in numerous preclinical and clinical studies.
- Herpes simplex virus type 2 (HSV-2) has been engineered as an oncolytic virus (oHSV2) for cancer treatment.
Purpose of the Study:
- To investigate the antitumor efficacy of oHSV2 in mouse models of colon carcinoma.
- To evaluate the impact of oHSV2 on the tumor immune microenvironment and systemic immunity.
- To assess the potential of oHSV2 in preventing tumor recurrence and metastasis.
Main Methods:
- Administration of oHSV2 in unilateral and bilateral mouse colon carcinoma models.
- Assessment of tumor growth, survival rates, and occurrence of side effects.
- Analysis of immune cell populations in the spleen and tumor microenvironment.
- Evaluation of immune memory response against tumor rechallenge and distant tumors.
Main Results:
- oHSV2 demonstrated significant antitumor efficacy, eliminating tumors and prolonging survival in mice.
- Treatment with oHSV2 prevented the growth of rechallenged and distant tumors, indicating immune memory.
- oHSV2 modulated the immune microenvironment by reducing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) while increasing natural killer (NK) cells, CD8+ T cells, and dendritic cells (DCs).
Conclusions:
- oHSV2 is a promising oncolytic virus for colon cancer therapy, effectively eliminating primary tumors and preventing metastasis.
- oHSV2 treatment establishes tumor-specific immunity and immune memory, crucial for long-term tumor control.
- The immunomodulatory effects of oHSV2 on the spleen and tumor microenvironment contribute to its enhanced therapeutic antitumor activity.
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