Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model
Our previous research verified that HSP (heat shock protein) 110 could enhance the anti-tumor effect of HPV16 E749-57 epitope. In this study, to optimize the immunotherapy of this vaccine type, we developed and evaluated the anti-tumor immunity of a nanoparticle vaccine format assembling with E749-5...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-10-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | http://dx.doi.org/10.1080/21645515.2021.1933875 |
| _version_ | 1827807624495628288 |
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| author | Yue Zhang Faliang Ren Bing Ni Tao Jing Jun Tang |
| author_facet | Yue Zhang Faliang Ren Bing Ni Tao Jing Jun Tang |
| author_sort | Yue Zhang |
| collection | DOAJ |
| description | Our previous research verified that HSP (heat shock protein) 110 could enhance the anti-tumor effect of HPV16 E749-57 epitope. In this study, to optimize the immunotherapy of this vaccine type, we developed and evaluated the anti-tumor immunity of a nanoparticle vaccine format assembling with E749-57-HSP110 fusion expression plasmid and RGD-GGG-K18 polypeptide. The nanoparticle vaccine was self-assembled from positively charged RGD-GGG-K18 polypeptide and negatively charged fusion expression plasmid pIRES2-3× E7-HSP110-EGFP. The particle size, stability, expression of E749-57-HSP110 fusion protein and the target ability of nanoparticle were determined, respectively. Specific CTL responses were determined by E7 tetramer staining and cytotoxicity assay in TC-1 tumor-bearing mice (CD4/CD8 knockout). The preventive and therapeutic experiments of nanoparticle vaccine were investigated in TC-1 tumor-bearing mice. Results showed that the RGD-GGG-K18 polypeptide and pIRES2-3× E7-HSP110-EGFP plasmid self-assembled nanoparticles about 100 nanometers in diameter when the charge ratios of peptide/plasmid were 2. The nanoparticles effectively entered TC-1 cells directed by RGD target-peptide, and correctly expressed the E7-HSP110 fusion protein. The HSP110 effectively facilitated nanoparticles activating CD8+T cells than nanoparticles without HSP110, including the CD8+ T cell number and the IFN-γ level; in contrast, the CD4+T cells immune response remained indiscriminate among the mice groups. This nanoparticle formulation inhibited tumor growth and prolonged the survival duration in the prophylactic and therapeutic mouse models. Therefore, the RGD-based tumor-targeting nanoparticle expressing E749-57-HSP110 fusion protein can efficiently evoke anti-tumor activity and thus suggests it might be a favorable candidate for cervical cancer immunotherapy. |
| first_indexed | 2024-03-11T22:00:02Z |
| format | Article |
| id | doaj.art-cf5a0410e38d485a97d0772e552ce6a0 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:00:02Z |
| publishDate | 2021-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-cf5a0410e38d485a97d0772e552ce6a02023-09-25T11:25:31ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2021-10-0117103529353810.1080/21645515.2021.19338751933875Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse modelYue Zhang0Faliang Ren1Bing Ni2Tao Jing3Jun Tang4University of Science and Technology of ChinaChildren’s Hospital of Chongqing Medical UniversityThird Military Medical UniversityThird Military Medical UniversityUniversity of Science and Technology of ChinaOur previous research verified that HSP (heat shock protein) 110 could enhance the anti-tumor effect of HPV16 E749-57 epitope. In this study, to optimize the immunotherapy of this vaccine type, we developed and evaluated the anti-tumor immunity of a nanoparticle vaccine format assembling with E749-57-HSP110 fusion expression plasmid and RGD-GGG-K18 polypeptide. The nanoparticle vaccine was self-assembled from positively charged RGD-GGG-K18 polypeptide and negatively charged fusion expression plasmid pIRES2-3× E7-HSP110-EGFP. The particle size, stability, expression of E749-57-HSP110 fusion protein and the target ability of nanoparticle were determined, respectively. Specific CTL responses were determined by E7 tetramer staining and cytotoxicity assay in TC-1 tumor-bearing mice (CD4/CD8 knockout). The preventive and therapeutic experiments of nanoparticle vaccine were investigated in TC-1 tumor-bearing mice. Results showed that the RGD-GGG-K18 polypeptide and pIRES2-3× E7-HSP110-EGFP plasmid self-assembled nanoparticles about 100 nanometers in diameter when the charge ratios of peptide/plasmid were 2. The nanoparticles effectively entered TC-1 cells directed by RGD target-peptide, and correctly expressed the E7-HSP110 fusion protein. The HSP110 effectively facilitated nanoparticles activating CD8+T cells than nanoparticles without HSP110, including the CD8+ T cell number and the IFN-γ level; in contrast, the CD4+T cells immune response remained indiscriminate among the mice groups. This nanoparticle formulation inhibited tumor growth and prolonged the survival duration in the prophylactic and therapeutic mouse models. Therefore, the RGD-based tumor-targeting nanoparticle expressing E749-57-HSP110 fusion protein can efficiently evoke anti-tumor activity and thus suggests it might be a favorable candidate for cervical cancer immunotherapy.http://dx.doi.org/10.1080/21645515.2021.1933875hsp110nanoparticle vaccinecervical cancerhpv16 e7rgd |
| spellingShingle | Yue Zhang Faliang Ren Bing Ni Tao Jing Jun Tang Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model Human Vaccines & Immunotherapeutics hsp110 nanoparticle vaccine cervical cancer hpv16 e7 rgd |
| title | Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model |
| title_full | Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model |
| title_fullStr | Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model |
| title_full_unstemmed | Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model |
| title_short | Tumor targeting nanoparticle E749-57-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model |
| title_sort | tumor targeting nanoparticle e749 57 hsp110 rgd elicits potent anti tumor immune response in a cd8 dependent manner in cervical cancer bearing mouse model |
| topic | hsp110 nanoparticle vaccine cervical cancer hpv16 e7 rgd |
| url | http://dx.doi.org/10.1080/21645515.2021.1933875 |
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