Skin Delivery of Clec4a Small Hairpin RNA Elicited an Effective Antitumor Response by Enhancing CD8+ Immunity In Vivo

Tzu Yang Weng, Chia Jung Li, Chung Yen Li, Yu Hsuan Hung, Meng Chi Yen, Yu Wei Chang, Yu Hung Chen, Yi Ling Chen, Hui Ping Hsu, Jang Yang Chang, Ming Derg Lai

研究成果: Article

摘要

Clec4a has been reported to be an immune suppressor of dendritic cells (DCs), but its potential role in cancer therapy remains to be elucidated. The present study investigated whether downregulating the expression of Clec4a via skin delivery of small hairpin RNA (shRNA) using a gene gun produced stronger host immunity and inhibited tumor progression in animal models. Administration of Clec4a2 shRNA delayed tumor growth in both mouse bladder and lung tumor-bearing mouse models. The result was further confirmed with a compensation experiment showing that the antitumor effects induced by Clec4a2 shRNA were restored by co-injection of a plasmid expressing exogenous Clec4a2. Increased numbers of infiltrating CD4+ and CD8+ T cells at tumor sites were observed in mice treated with Clec4a2 shRNA. Splenocytes from mice with Clec4a2 shRNA administration exhibited stronger cytotoxic activity compared with splenocytes from control mice. CD8-deletion in vivo abrogated the antitumor effects elicited by Clec4a2 shRNA. Additionally, shClec4a enhanced the antitumor effects of the Neu DNA vaccine in the MBT-2 tumor model. In summary, the findings provide evidence that silencing of Clec4a2 expression via skin delivery of shRNA produces an effective antitumor response and that Clec4a2 shRNA may have therapeutic potential as an adjuvant for cancer immunotherapy.

原文English
頁(從 - 到)419-427
頁數9
期刊Molecular Therapy - Nucleic Acids
9
DOIs
出版狀態Published - 2017 十二月

指紋

Small Interfering RNA
Immunity
Skin
Neoplasms
DNA Vaccines
Firearms
Urinary Bladder Neoplasms
Immunotherapy
Dendritic Cells
Plasmids
Down-Regulation
Animal Models
T-Lymphocytes
Lung
Injections
Therapeutics
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

引用此文

Weng, Tzu Yang ; Li, Chia Jung ; Li, Chung Yen ; Hung, Yu Hsuan ; Yen, Meng Chi ; Chang, Yu Wei ; Chen, Yu Hung ; Chen, Yi Ling ; Hsu, Hui Ping ; Chang, Jang Yang ; Lai, Ming Derg. / Skin Delivery of Clec4a Small Hairpin RNA Elicited an Effective Antitumor Response by Enhancing CD8+ Immunity In Vivo. 於: Molecular Therapy - Nucleic Acids. 2017 ; 卷 9. 頁 419-427.
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abstract = "Clec4a has been reported to be an immune suppressor of dendritic cells (DCs), but its potential role in cancer therapy remains to be elucidated. The present study investigated whether downregulating the expression of Clec4a via skin delivery of small hairpin RNA (shRNA) using a gene gun produced stronger host immunity and inhibited tumor progression in animal models. Administration of Clec4a2 shRNA delayed tumor growth in both mouse bladder and lung tumor-bearing mouse models. The result was further confirmed with a compensation experiment showing that the antitumor effects induced by Clec4a2 shRNA were restored by co-injection of a plasmid expressing exogenous Clec4a2. Increased numbers of infiltrating CD4+ and CD8+ T cells at tumor sites were observed in mice treated with Clec4a2 shRNA. Splenocytes from mice with Clec4a2 shRNA administration exhibited stronger cytotoxic activity compared with splenocytes from control mice. CD8-deletion in vivo abrogated the antitumor effects elicited by Clec4a2 shRNA. Additionally, shClec4a enhanced the antitumor effects of the Neu DNA vaccine in the MBT-2 tumor model. In summary, the findings provide evidence that silencing of Clec4a2 expression via skin delivery of shRNA produces an effective antitumor response and that Clec4a2 shRNA may have therapeutic potential as an adjuvant for cancer immunotherapy.",
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Skin Delivery of Clec4a Small Hairpin RNA Elicited an Effective Antitumor Response by Enhancing CD8+ Immunity In Vivo. / Weng, Tzu Yang; Li, Chia Jung; Li, Chung Yen; Hung, Yu Hsuan; Yen, Meng Chi; Chang, Yu Wei; Chen, Yu Hung; Chen, Yi Ling; Hsu, Hui Ping; Chang, Jang Yang; Lai, Ming Derg.

於: Molecular Therapy - Nucleic Acids, 卷 9, 12.2017, p. 419-427.

研究成果: Article

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AU - Weng, Tzu Yang

AU - Li, Chia Jung

AU - Li, Chung Yen

AU - Hung, Yu Hsuan

AU - Yen, Meng Chi

AU - Chang, Yu Wei

AU - Chen, Yu Hung

AU - Chen, Yi Ling

AU - Hsu, Hui Ping

AU - Chang, Jang Yang

AU - Lai, Ming Derg

PY - 2017/12

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AB - Clec4a has been reported to be an immune suppressor of dendritic cells (DCs), but its potential role in cancer therapy remains to be elucidated. The present study investigated whether downregulating the expression of Clec4a via skin delivery of small hairpin RNA (shRNA) using a gene gun produced stronger host immunity and inhibited tumor progression in animal models. Administration of Clec4a2 shRNA delayed tumor growth in both mouse bladder and lung tumor-bearing mouse models. The result was further confirmed with a compensation experiment showing that the antitumor effects induced by Clec4a2 shRNA were restored by co-injection of a plasmid expressing exogenous Clec4a2. Increased numbers of infiltrating CD4+ and CD8+ T cells at tumor sites were observed in mice treated with Clec4a2 shRNA. Splenocytes from mice with Clec4a2 shRNA administration exhibited stronger cytotoxic activity compared with splenocytes from control mice. CD8-deletion in vivo abrogated the antitumor effects elicited by Clec4a2 shRNA. Additionally, shClec4a enhanced the antitumor effects of the Neu DNA vaccine in the MBT-2 tumor model. In summary, the findings provide evidence that silencing of Clec4a2 expression via skin delivery of shRNA produces an effective antitumor response and that Clec4a2 shRNA may have therapeutic potential as an adjuvant for cancer immunotherapy.

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