Fully human anti-B7-H3 recombinant antibodies inhibited tumor growth by increasing T cell infiltration
Copyright © 2024 Elsevier B.V. All rights reserved..
Mortality due to malignant tumors is one of the major factors affecting the life expectancy of the global population. Therapeutic antibodies are a cutting-edge treatment method for restricting tumor growth. B7-H3 is highly expressed in tumor tissues, but rarely in normal tissues. B7-H3 is closely associated with poor prognosis in patients with tumors. B7-H3 is an important target for antitumor therapy. In this study, the fully human anti-B7H3 single-chain antibodies (scFvs) were isolated and screened from the fully human phage immune library with B7H3 as the target. The antibodies screened from a fully human phage library had low immunogenicity and high affinity, which was more beneficial for clinical application. Leveraging B7-H3 scFvs as a foundation, we constructed two distinct recombinant antibody formats, scFv-Fc and IgG1, characterized by elevated affinity and a prolonged half-life. The results demonstrated that the recombinant antibodies had high specificity and affinity for the B7-H3 antigen and inhibited tumor cell growth by enhancing the ADCC. After treatment with anti-B7H3 recombinant antibody, the number of infiltrating T cells in the tumor increased and the secretion of IFN- γ by infiltrating T cells increased in vivo. Additionally, the use of pleural fluid samples obtained from tumor-afflicted patients revealed the ability of anti-B7-H3 recombinant antibodies to reverse CD8+ T cell exhaustion. In summary, we screened the fully human anti-B7H3 recombinant antibodies with specificity and high affinity that increase immune cell infiltration and IFN-γ secretion, thereby inhibiting tumor cell growth to a certain extent. This finding provides a theoretical basis for the development of therapeutic tumor antibodies and could help promote further development of antibody-based drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:132 |
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| Enthalten in: |
International immunopharmacology - 132(2024) vom: 28. März, Seite 111926 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Lin [VerfasserIn] |
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| Links: |
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| Themen: |
B7-H3 |
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| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.intimp.2024.111926 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Mortality due to malignant tumors is one of the major factors affecting the life expectancy of the global population. Therapeutic antibodies are a cutting-edge treatment method for restricting tumor growth. B7-H3 is highly expressed in tumor tissues, but rarely in normal tissues. B7-H3 is closely associated with poor prognosis in patients with tumors. B7-H3 is an important target for antitumor therapy. In this study, the fully human anti-B7H3 single-chain antibodies (scFvs) were isolated and screened from the fully human phage immune library with B7H3 as the target. The antibodies screened from a fully human phage library had low immunogenicity and high affinity, which was more beneficial for clinical application. Leveraging B7-H3 scFvs as a foundation, we constructed two distinct recombinant antibody formats, scFv-Fc and IgG1, characterized by elevated affinity and a prolonged half-life. The results demonstrated that the recombinant antibodies had high specificity and affinity for the B7-H3 antigen and inhibited tumor cell growth by enhancing the ADCC. After treatment with anti-B7H3 recombinant antibody, the number of infiltrating T cells in the tumor increased and the secretion of IFN- γ by infiltrating T cells increased in vivo. Additionally, the use of pleural fluid samples obtained from tumor-afflicted patients revealed the ability of anti-B7-H3 recombinant antibodies to reverse CD8+ T cell exhaustion. In summary, we screened the fully human anti-B7H3 recombinant antibodies with specificity and high affinity that increase immune cell infiltration and IFN-γ secretion, thereby inhibiting tumor cell growth to a certain extent. This finding provides a theoretical basis for the development of therapeutic tumor antibodies and could help promote further development of antibody-based drugs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a B7-H3 | |
| 650 | 4 | |a CD8(+) T cells | |
| 650 | 4 | |a Fully human antibodies | |
| 650 | 4 | |a Immune library | |
| 650 | 4 | |a Immunoinfiltration | |
| 650 | 4 | |a Tumor therapy | |
| 700 | 1 | |a Nian, Siji |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Jimu, Wulemo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chengwen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhanwen |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qiaosen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yuanshuai |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Qing |e verfasserin |4 aut | |
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