Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine
| Autor: | Shuping Yuan, Tingting Chen, Zhiwen Yang, Wenyi Zou, Guimiao Lin, Xiaomei Wang, Jiangyao Xu, Christina C.N. Wu, Maixian Liu, Kan Liu, Li Li, Dennis A. Carson, Tianying Zhan |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research medicine.medical_treatment chemical and pharmacologic phenomena Biology cancer immunology Cancer Vaccines lcsh:RC254-282 Epitopes Mice 03 medical and health sciences Immunogenicity Vaccine 0302 clinical medicine Immune system Adjuvants Immunologic Antigen Antigens Neoplasm Cell Line Tumor Neoplasms medicine Animals Humans Cytotoxic T cell oct4 Cancer immunology Vaccines Synthetic cancer prevention Acquired immune system lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Disease Models Animal 030104 developmental biology Oncology Toll-Like Receptor 9 030220 oncology & carcinogenesis Hemocyanins Neoplastic Stem Cells Cancer research biology.protein Original Article Cancer vaccine Peptides Octamer Transcription Factor-3 Adjuvant Keyhole limpet hemocyanin tlr9 agonist |
| Zdroj: | Cancer Biology & Medicine, Vol 17, Iss 1, Pp 132-141 (2020) Cancer Biology & Medicine |
| ISSN: | 2095-3941 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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