Cargando…
A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma
BACKGROUND: The immune non-recognition is often the underlying cause of failure in tumor immunotherapeutic. This is because most tumor-related antigens are poorly immunogenic, and fail to arouse an efficient immune response against cancers. Here we synthesized a novel TLR7 agonist, and developed a s...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455914/ https://www.ncbi.nlm.nih.gov/pubmed/25990580 http://dx.doi.org/10.1186/s12967-015-0524-y |
_version_ | 1782374785579220992 |
---|---|
author | Lin, Guimiao Wang, Xiaomei Yi, Wanxian Zhang, Chuanxia Xu, Gaixia Zhu, Xiaomei Cai, Zhiming Liu, Yu Diao, Yuwen Lin, Marie Chia-Mi Jin, Guangyi |
author_facet | Lin, Guimiao Wang, Xiaomei Yi, Wanxian Zhang, Chuanxia Xu, Gaixia Zhu, Xiaomei Cai, Zhiming Liu, Yu Diao, Yuwen Lin, Marie Chia-Mi Jin, Guangyi |
author_sort | Lin, Guimiao |
collection | PubMed |
description | BACKGROUND: The immune non-recognition is often the underlying cause of failure in tumor immunotherapeutic. This is because most tumor-related antigens are poorly immunogenic, and fail to arouse an efficient immune response against cancers. Here we synthesized a novel TLR7 agonist, and developed a safe and effective immunotherapeutic vaccine by conjugating this TLR7 agonist with the pluripotency antigen OCT4. METHODS: Purified recombinant OCT4 protein was covalently linked with a novel TLR7 agonist to form a TLR7-OCT4 conjugate (T7-OCT4). After conjugation, the in vitro release of IL-12 and IFN-γ was observed in spleen lymphocytes. Mice were immunized with TLR7-OCT4, and the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the OCT4-specific cytotoxicity rates were measured. The immunized mice were challenged with mouse embryonic carcinoma (EC), and the tumor volume and tumor weight were determined. Blood routine examination was performed to evaluate the biosafety of TLR7 agonist and TLR7-OCT4 conjugate in mice. RESULTS: T7-OCT4 conjugate significantly increased the in vitro release of IL-12 and IFN-γ by mouse spleen lymphocytes. In addition, the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the tumor-specific cytotoxicity rates in immunized mice were significantly higher. Importantly, in EC xenografted mice, immunization with T7-OCT4 conjugate decreased the growth of the tumor dramatically up to 90 %, as compared to mice immunized with OCT4 protein or TLR7 agonist alone. Furthermore, blood routine examination demonstrated that no abnormalities of the blood cells and components in the blood fluids were detected by T7-OCT4 and TLR7 agonist injections. CONCLUSIONS: Our results showed that conjugating OCT4 protein to the novel TLR7 agonist produced a vaccine which is effective and safe in preventing tumor growth in mice. Our results suggest that this type of vaccine formulation has great potentiality in preventive vaccines against OCT4 expressing tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0524-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4455914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44559142015-06-05 A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma Lin, Guimiao Wang, Xiaomei Yi, Wanxian Zhang, Chuanxia Xu, Gaixia Zhu, Xiaomei Cai, Zhiming Liu, Yu Diao, Yuwen Lin, Marie Chia-Mi Jin, Guangyi J Transl Med Research BACKGROUND: The immune non-recognition is often the underlying cause of failure in tumor immunotherapeutic. This is because most tumor-related antigens are poorly immunogenic, and fail to arouse an efficient immune response against cancers. Here we synthesized a novel TLR7 agonist, and developed a safe and effective immunotherapeutic vaccine by conjugating this TLR7 agonist with the pluripotency antigen OCT4. METHODS: Purified recombinant OCT4 protein was covalently linked with a novel TLR7 agonist to form a TLR7-OCT4 conjugate (T7-OCT4). After conjugation, the in vitro release of IL-12 and IFN-γ was observed in spleen lymphocytes. Mice were immunized with TLR7-OCT4, and the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the OCT4-specific cytotoxicity rates were measured. The immunized mice were challenged with mouse embryonic carcinoma (EC), and the tumor volume and tumor weight were determined. Blood routine examination was performed to evaluate the biosafety of TLR7 agonist and TLR7-OCT4 conjugate in mice. RESULTS: T7-OCT4 conjugate significantly increased the in vitro release of IL-12 and IFN-γ by mouse spleen lymphocytes. In addition, the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the tumor-specific cytotoxicity rates in immunized mice were significantly higher. Importantly, in EC xenografted mice, immunization with T7-OCT4 conjugate decreased the growth of the tumor dramatically up to 90 %, as compared to mice immunized with OCT4 protein or TLR7 agonist alone. Furthermore, blood routine examination demonstrated that no abnormalities of the blood cells and components in the blood fluids were detected by T7-OCT4 and TLR7 agonist injections. CONCLUSIONS: Our results showed that conjugating OCT4 protein to the novel TLR7 agonist produced a vaccine which is effective and safe in preventing tumor growth in mice. Our results suggest that this type of vaccine formulation has great potentiality in preventive vaccines against OCT4 expressing tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0524-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-20 /pmc/articles/PMC4455914/ /pubmed/25990580 http://dx.doi.org/10.1186/s12967-015-0524-y Text en © Lin et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lin, Guimiao Wang, Xiaomei Yi, Wanxian Zhang, Chuanxia Xu, Gaixia Zhu, Xiaomei Cai, Zhiming Liu, Yu Diao, Yuwen Lin, Marie Chia-Mi Jin, Guangyi A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title | A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title_full | A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title_fullStr | A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title_full_unstemmed | A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title_short | A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
title_sort | conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455914/ https://www.ncbi.nlm.nih.gov/pubmed/25990580 http://dx.doi.org/10.1186/s12967-015-0524-y |
work_keys_str_mv | AT linguimiao aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT wangxiaomei aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT yiwanxian aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT zhangchuanxia aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT xugaixia aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT zhuxiaomei aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT caizhiming aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT liuyu aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT diaoyuwen aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT linmariechiami aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT jinguangyi aconjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT linguimiao conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT wangxiaomei conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT yiwanxian conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT zhangchuanxia conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT xugaixia conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT zhuxiaomei conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT caizhiming conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT liuyu conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT diaoyuwen conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT linmariechiami conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma AT jinguangyi conjugateofoctamerbindingtranscriptionfactor4andtolllikereceptor7agonistpreventsthegrowthandmetastasisoftestisembryoniccarcinoma |