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Novel Protocol for Generating Physiologic Immunogenic Dendritic Cells
Published on: May 17, 2019
Enhanced immunotherapeutic effect of modified HPV16 E7-pulsed dendritic cell vaccine by an adeno-shRNA-SOCS1 virus
Yongqiang Zhu1, Yi Zheng, Lin Mei
1School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
Abstract:
Cervical cancer is the second most common cause of cancer-related deaths among women worldwide. However, no efficient therapy exists against cervical cancer and current treatments have several disadvantages. One possible novel approach is to develop immune-based strategies using tumor antigen-loaded dendritic cells (DCs) for the induction of cellular antitumor immunity. In this study, we created a modified HPV16 E7, HPV16mE7, to reduce its transformation activity and to enhance its antigenicity. The siRNA delivery technique was used to silence the suppressor of cytokine signaling 1 (SOCS1) gene in DCs. BM-derived DCs infected by ad-shRNA-SOCS1 were pulsed with the HPV16mE7 protein and then were transfused into mouse models bearing TC-1 tumor cells expressing HPV16 E6/E7. IFN-γ, cytokine (TNF-α, IL-12, IL-6) expression, anti-E7 antibody and cytotoxic T lymphocyte (CTL) levels were measured. The survival rate, survival days and the tumor volume of the mouse models from the different treatment groups were monitored. The data showed that the mE7-pulsed DC vaccine enhanced by adenovirus-mediated SOCS1 silencing exhibited better immunotherapeutic effect on the allografted tumor mouse models. The method by silencing SOCS1 in HPV16mE7 protein-pulsed DCs may provide a new strategy for the development of safe and effective immunotherapy for cervical cancer.
Insights
This study developed a novel immunotherapy for cervical cancer using modified tumor antigens and dendritic cells. Silencing the SOCS1 gene in dendritic cells enhanced the anti-tumor immune response in mouse models, improving survival rates.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cervical cancer is a leading cause of cancer deaths in women globally.
- Current therapies for cervical cancer are limited and have significant drawbacks.
- Developing effective immunotherapies, such as dendritic cell (DC)-based vaccines, is a promising strategy.
Purpose of the Study:
- To create a modified HPV16 E7 antigen (HPV16mE7) with reduced transformation activity and enhanced antigenicity.
- To investigate the efficacy of silencing the suppressor of cytokine signaling 1 (SOCS1) gene in DCs using siRNA delivery.
- To evaluate the therapeutic potential of HPV16mE7-pulsed DCs with silenced SOCS1 in a mouse model of cervical cancer.
Main Methods:
- Generated a modified HPV16 E7 protein (HPV16mE7).
- Utilized siRNA delivery to silence the SOCS1 gene in bone marrow-derived DCs (BM-DCs).
- Pulsed SOCS1-silenced BM-DCs with HPV16mE7 and administered them to TC-1 tumor-bearing mouse models.
Main Results:
- Adenovirus-mediated SOCS1 silencing in HPV16mE7-pulsed DCs significantly enhanced anti-tumor immunity.
- Increased levels of IFN-γ, TNF-α, IL-12, and IL-6 cytokines were observed.
- Elevated anti-E7 antibody titers and cytotoxic T lymphocyte (CTL) activity were detected.
- Treatment resulted in improved survival rates and reduced tumor volume in the mouse models.
Conclusions:
- Silencing SOCS1 in HPV16mE7-pulsed DCs offers a potent immunotherapeutic strategy.
- This approach demonstrates a promising new avenue for developing safe and effective cervical cancer immunotherapies.
- The findings support the potential of combining antigen modification with immune gene silencing for cancer treatment.
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