論文 - 詳細
| RRC ID | 57860 |
|---|---|
| 著者 | Kurosawa N, Wakata Y, Ida K, Midorikawa A, Isobe M. |
| タイトル | High throughput development of TCR-mimic antibody that targets survivin-2B80-88/HLA-A*A24 and its application in a bispecific T-cell engager. |
| ジャーナル | Sci Rep |
| Abstract |
Intracellular tumor-associated antigens are targeted by antibodies known as T-cell receptor mimic antibodies (TCRm-Abs), which recognize T-cell epitopes with better stabilities and higher affinities than T-cell receptors. However, TCRm-Abs have been proven difficult to produce using conventional techniques. Here, we developed TCRm-Abs that recognize the survivin-2B-derived nonamer peptide, AYACNTSTL (SV2B80-88), presented on HLA-A*24 (SV2B80-88/HLA-A*24) from immunized mice by using a fluorescence-activated cell sorting-based antigen-specific plasma cells isolation method combined with a high-throughput single-cell-based immunoglobulin-gene-cloning technology. This approach yielded a remarkable efficiency in generating candidate antibody clones that recognize SV2B80-88/HLA-A*24. The screening of the antibody clones for their affinity and ability to bind key amino-acid residues within the target peptide revealed that one clone, #21-3, specifically recognized SV2B80-88/HLA-A*24 on T2 cells. The specificity of #21-3 was further established through survivin-2B-positive tumor cell lines that exogenously or endogenously express HLA-A*24. A bispecific T-cell engager comprised of #21-3 and anti-CD3 showed specific cytotoxicity towards cells bearing SV2B80-88/HLA-A*24 by recruiting and activating T-cells in vitro. The efficient development of TCRm-Ab overcomes the limitations that hamper antibody-based immunotherapeutic approaches and enables the targeting of intracellular tumor-associated antigens. |
| 巻・号 | 9(1) |
| ページ | 9827 |
| 公開日 | 2019-7-8 |
| DOI | 10.1038/s41598-019-46198-5 |
| PII | 10.1038/s41598-019-46198-5 |
| PMID | 31285464 |
| PMC | PMC6614450 |
| MeSH | Animals Antibodies, Bispecific / metabolism* Cell Separation Epitopes, T-Lymphocyte / immunology Flow Cytometry HLA-A24 Antigen / immunology* HeLa Cells High-Throughput Screening Assays Humans Immunization Leukocytes, Mononuclear / cytology Mice Receptors, Antigen, T-Cell / immunology* Survivin / immunology* |
| IF | 3.998 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) Jurkat(RCB3052) COLO-320(RCB1193) |