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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin
Zhiwei Zhao1, Yaqin Yao, Zhenyu Ding
1State Key Laboratory of Biotherapy, West China Hospital and College of Life Science, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, People's Republic of China.
Abstract:
Anti-angiogenesis represents an indispensible strategy for cancer therapy. As a strictly endothelial-specific adhesion molecule, vascular endothelial cadherin (VE-cadherin, VE-cad) is a promising anti-angiogenesis target. In this study a recombinant adenovirus vector modified with mannan was used to deliver VE-cad (AdVEC-m) and we tried to explore its feasibility as an antitumour agent in mouse cancer models. The immunogenic delivery of VE-cad resulted in obvious prophylactic and therapeutic inhibition of tumour growth and prolonged survival in mice. In the meantime angiogenesis declined apparently within the tumours measured by immunohistochemistry staining and coated alginate bead assay in vivo. Anti-VE-cad antibodies were identified by western blot analysis and enzyme-linked immunosorbent assay (ELISA). VE-cad-specific T lymphocyte cytotoxicity responses (CTL) were detected by chromium (51Cr) release assay of splenocytes from AdVEC-m treated mice. These results demonstrate that mannan modification is able to enhance antigen delivery and immune responses, and the way of immunogenic delivery (AdVEC-m) is expected to provide an attractive vaccine strategy for cancer immunotherapy.
Insights
This study shows that delivering vascular endothelial cadherin (VE-cadherin) using a modified adenovirus vector (AdVEC-m) effectively inhibits tumor growth and angiogenesis in mice. This approach offers a promising cancer vaccine strategy by enhancing immune responses.
Area of Science:
- Oncology
- Immunology
- Gene Therapy
Background:
- Anti-angiogenesis is crucial for cancer therapy.
- Vascular endothelial cadherin (VE-cadherin) is a specific target for anti-angiogenesis strategies.
- Developing effective cancer immunotherapies is an ongoing challenge.
Purpose of the Study:
- To evaluate the anti-tumor potential of immunogenic delivery of VE-cadherin.
- To assess the efficacy of a mannan-modified adenovirus vector (AdVEC-m) for delivering VE-cadherin.
- To explore AdVEC-m as a cancer vaccine strategy.
Main Methods:
- Utilized a recombinant adenovirus vector modified with mannan to deliver VE-cadherin (AdVEC-m).
- Assessed tumor growth inhibition, survival rates, and angiogenesis in mouse cancer models.
- Employed immunohistochemistry, coated alginate bead assay, western blot, ELISA, and 51Cr release assay to measure immune responses and anti-VE-cadherin antibodies.
Main Results:
- AdVEC-m demonstrated significant prophylactic and therapeutic inhibition of tumor growth.
- A notable decline in tumor angiogenesis was observed.
- VE-cadherin-specific T lymphocyte cytotoxicity responses were detected, indicating an effective immune response.
- Mannan modification enhanced antigen delivery and immune responses.
Conclusions:
- Immunogenic delivery of VE-cadherin via AdVEC-m is a feasible anti-cancer strategy.
- Mannan modification enhances antigen delivery and immune stimulation.
- This approach represents a promising vaccine strategy for cancer immunotherapy.
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