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Updated: Jun 29, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Fully human anti-B7-H3 recombinant antibodies inhibited tumor growth by increasing T cell infiltration
1The School of Basic Medical Sciences, Public Center of Experimental Technology, Southwest Medical University, Luzhou, Sichuan province 646000, China.
Abstract:
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.
Insights
Researchers developed fully human anti-B7H3 antibodies to combat cancer. These therapeutic antibodies show high affinity and specificity, enhancing immune responses to inhibit tumor growth and reverse T cell exhaustion.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Malignant tumors significantly impact global life expectancy.
- B7-H3 is a tumor-associated antigen crucial for antitumor therapy due to its high expression in tumors and association with poor prognosis.
- Therapeutic antibodies represent a promising strategy for cancer treatment.
Purpose of the Study:
- To isolate and characterize fully human anti-B7H3 single-chain variable fragments (scFvs) from a phage immune library.
- To develop recombinant antibody formats (scFv-Fc and IgG1) with enhanced affinity and half-life for improved clinical application.
- To evaluate the efficacy of these recombinant antibodies in inhibiting tumor growth and modulating the tumor immune microenvironment.
Main Methods:
- Screening of a fully human phage immune library to identify anti-B7H3 scFvs.
- Construction and characterization of recombinant anti-B7H3 scFv-Fc and IgG1 antibodies.
- Assessment of antibody specificity, affinity, and tumor cell growth inhibition, including antibody-dependent cell-mediated cytotoxicity (ADCC).
- In vivo studies evaluating immune cell infiltration, interferon-gamma (IFN-γ) secretion, and reversal of CD8+ T cell exhaustion using patient-derived samples.
Main Results:
- Isolated fully human anti-B7H3 scFvs with high affinity and low immunogenicity.
- Developed recombinant antibodies (scFv-Fc and IgG1) exhibiting enhanced affinity and prolonged half-life.
- Demonstrated significant inhibition of tumor cell growth mediated by enhanced ADCC.
- Observed increased T cell infiltration and IFN-γ secretion in tumors post-treatment.
- Showed that anti-B7H3 antibodies can reverse CD8+ T cell exhaustion in patient samples.
Conclusions:
- Fully human anti-B7H3 recombinant antibodies were successfully developed with high specificity and affinity.
- These antibodies effectively inhibit tumor cell growth by enhancing immune cell infiltration and IFN-γ secretion.
- The findings provide a strong theoretical basis for developing novel antibody-based cancer therapeutics.
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