Potent anti-tumor immune response and tumor growth inhibition induced by HER2 subdomain fusion protein in a mouse tumor model
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
PURPOSE: Several approaches have so far been employed to establish anti-tumor immunity by targeting HER2 protein. Active immunization with recombinant HER2 subdomains has previously been demonstrated to induce potent immune response and tumor growth inhibition. In the present study, we investigated the immunogenicity and tumor inhibitory effect of a fusion protein consisting of human HER2 extracellular subdomain (ECD-DI + II) together with T-helper cell epitopes of Tetanus toxin (p2 and p30).
METHODS: BALB/c mice were immunized with two recombinant proteins (DI + II and p2p30-DI + II) emulsified in 4 different adjuvants. Anti-DI + II antibody response, cytokine profile, frequency of splenic CD25+FOXP3+ regulatory T cells (Tregs) and CD8+CD107a+ cytotoxic T lymphocytes (CTLs) were assessed in the immunized mice. To assess the anti-tumor effect, the immunized mice were subcutaneously challenged with HER2-overexpressing tumor cells and the tumor growth was determined.
RESULTS: Both recombinant proteins were able to induce comparable levels of ECD-DI + II-specific antibodies. Immunization with p2p30-DI + II resulted in a significant increase in the level of Interferon-gamma (IFN-γ) secretion compared to DI + II protein and significantly higher frequency of CTLs and lower frequency of Tregs. The number of mice that remained tumor-free until day 120 was significantly higher in p2p30-DI + II vaccinated groups.
CONCLUSIONS: Our data suggest that the p2p30-DI + II fusion protein together with CpG adjuvant induces more potent anti-tumor immune responses in a mouse tumor model. Accordingly, this formulation might be considered as a potential immunotherapeutic approach in HER2+ cancers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:149 |
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| Enthalten in: |
Journal of cancer research and clinical oncology - 149(2023), 6 vom: 08. Juni, Seite 2437-2450 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ghaedi, Mojgan [VerfasserIn] |
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| Links: |
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| Themen: |
Active immunotherapy |
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| Anmerkungen: |
Date Completed 27.04.2023 Date Revised 27.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00432-022-04084-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Potent anti-tumor immune response and tumor growth inhibition induced by HER2 subdomain fusion protein in a mouse tumor model |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a PURPOSE: Several approaches have so far been employed to establish anti-tumor immunity by targeting HER2 protein. Active immunization with recombinant HER2 subdomains has previously been demonstrated to induce potent immune response and tumor growth inhibition. In the present study, we investigated the immunogenicity and tumor inhibitory effect of a fusion protein consisting of human HER2 extracellular subdomain (ECD-DI + II) together with T-helper cell epitopes of Tetanus toxin (p2 and p30) | ||
| 520 | |a METHODS: BALB/c mice were immunized with two recombinant proteins (DI + II and p2p30-DI + II) emulsified in 4 different adjuvants. Anti-DI + II antibody response, cytokine profile, frequency of splenic CD25+FOXP3+ regulatory T cells (Tregs) and CD8+CD107a+ cytotoxic T lymphocytes (CTLs) were assessed in the immunized mice. To assess the anti-tumor effect, the immunized mice were subcutaneously challenged with HER2-overexpressing tumor cells and the tumor growth was determined | ||
| 520 | |a RESULTS: Both recombinant proteins were able to induce comparable levels of ECD-DI + II-specific antibodies. Immunization with p2p30-DI + II resulted in a significant increase in the level of Interferon-gamma (IFN-γ) secretion compared to DI + II protein and significantly higher frequency of CTLs and lower frequency of Tregs. The number of mice that remained tumor-free until day 120 was significantly higher in p2p30-DI + II vaccinated groups | ||
| 520 | |a CONCLUSIONS: Our data suggest that the p2p30-DI + II fusion protein together with CpG adjuvant induces more potent anti-tumor immune responses in a mouse tumor model. Accordingly, this formulation might be considered as a potential immunotherapeutic approach in HER2+ cancers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Active immunotherapy | |
| 650 | 4 | |a Fusion protein | |
| 650 | 4 | |a HER2 | |
| 650 | 4 | |a Tetanus toxin | |
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| 700 | 1 | |a Khoshnoodi, Jalal |e verfasserin |4 aut | |
| 700 | 1 | |a Mortezagholi, Sahar |e verfasserin |4 aut | |
| 700 | 1 | |a Jeddi-Tehrani, Mahmood |e verfasserin |4 aut | |
| 700 | 1 | |a Amiri, Mohammad Mehdi |e verfasserin |4 aut | |
| 700 | 1 | |a Shokri, Fazel |e verfasserin |4 aut | |
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