Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine
Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ ce...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2020-02-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1571 |
| _version_ | 1818137030443401216 |
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| author | Tingting Chen Kan Liu Jiangyao Xu Tianying Zhan Maixian Liu Li Li Zhiwen Yang Shuping Yuan Wenyi Zou Guimiao Lin Dennis A. Carson Christina C. N. Wu Xiaomei Wang |
| author_facet | Tingting Chen Kan Liu Jiangyao Xu Tianying Zhan Maixian Liu Li Li Zhiwen Yang Shuping Yuan Wenyi Zou Guimiao Lin Dennis A. Carson Christina C. N. Wu Xiaomei Wang |
| author_sort | Tingting Chen |
| collection | DOAJ |
| description | Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development. Methods: To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9). Results: Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P < 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), IL-2 (P < 0.01), and IL-6 (P < 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines. Conclusions: Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma. |
| first_indexed | 2024-12-11T09:49:49Z |
| format | Article |
| id | doaj.art-1c314af84101402fb9b75ec9cd76fd9f |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-11T09:49:49Z |
| publishDate | 2020-02-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-1c314af84101402fb9b75ec9cd76fd9f2022-12-22T01:12:26ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412020-02-0117113214110.20892/j.issn.2095-3941.2019.0224Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccineTingting Chen0Kan Liu1Jiangyao Xu2Tianying Zhan3Maixian Liu4Li Li5Zhiwen Yang6Shuping Yuan7Wenyi Zou8Guimiao Lin9Dennis A. Carson10Christina C. N. Wu11Xiaomei Wang12Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen University, Shenzhen 518060, ChinaObjective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development. Methods: To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9). Results: Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P < 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), IL-2 (P < 0.01), and IL-6 (P < 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines. Conclusions: Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.http://www.cancerbiomed.org/index.php/cocr/article/view/1571cancer preventioncancer immunologyoct4tlr9 agonist |
| spellingShingle | Tingting Chen Kan Liu Jiangyao Xu Tianying Zhan Maixian Liu Li Li Zhiwen Yang Shuping Yuan Wenyi Zou Guimiao Lin Dennis A. Carson Christina C. N. Wu Xiaomei Wang Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine Cancer Biology & Medicine cancer prevention cancer immunology oct4 tlr9 agonist |
| title | Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine |
| title_full | Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine |
| title_fullStr | Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine |
| title_full_unstemmed | Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine |
| title_short | Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine |
| title_sort | synthetic and immunological studies on the oct4 immunodominant motif antigen based anti cancer vaccine |
| topic | cancer prevention cancer immunology oct4 tlr9 agonist |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1571 |
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