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Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

ABSTRACT: Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

SUBMITTER: Tang X

PROVIDER: S-EPMC11336886 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Tang Xueyi X He Linhai L Wang Xiaoli X Liu Shuaichao S Liu Xiangning X Shen Xiaorui X Shu Yun Y Yang Ke K Zhou Qionghua Q Shan Zujian Z Wang Yueming Y Wu Changwen C Jia Zhenxing Z Liu Tong T Wang Yayu Y Liao Hua-Xin HX Xia Yun Y

Heliyon 20240803 15

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cell ...[more]

PMID: 39170144

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Project description:BackgroundMonoclonal antibodies are essential in life science research and developing antibody drugs and test drugs. Various methods have been developed to obtain monoclonal antibodies, among which hybridoma technology continues to be widely used. However, developing a rapid and efficient method for obtaining conformation-specific antibodies using hybridoma technology remains challenging. We previously developed the membrane-type immunoglobulin-directed hybridoma screening (MIHS) method, which is a flow cytometry-based screening technique based on the interaction between the B-cell receptor expressed on the hybridoma cell surface and the antigen protein, to obtain conformation-specific antibodies.ResultsIn this study, we proposed a streptavidin-anchored ELISA screening technology (SAST) as a secondary screening method that retains the advantages of the MIHS method. Anti-enhanced green fluorescent protein monoclonal antibodies were generated as a model experiment, and their structural recognition abilities were examined. Examination of the reaction profiles showed that all monoclonal antibodies obtained in this study recognize the conformational epitopes of the protein antigen. Furthermore, these monoclonal antibodies were classified into two groups: those with binding activities against partially denatured proteins and those with complete loss of binding activities. Next, when screening monoclonal antibodies by the MIHS method as the first screening, we found that monoclonal antibodies with stronger binding constants may be selected by double-staining for hybridomas with fluorescently labeled target antigens and fluorescently labeled B cell receptor antibodies.ConclusionsThe proposed two-step screening method, which incorporates MIHS and SAST, constitutes a rapid, simple, and effective strategy to obtain conformation-specific monoclonal antibodies generated through hybridoma technology. The novel monoclonal antibody screening strategy reported herein could accelerate the development of antibody drugs and antibody tests.

Dataset Information

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Publications

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

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