Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1
Abstract The development of effective immunotherapies for solid tumors remains a significant challenge. In previous studies, we identified PVT1, a long non-coding RNA, with the peptide HF10 derived from PVT1, presented by HLA-A24. This study aims to develop a single-chain variable fragment (scFv) th...
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Springer
2025-03-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03976-7 |
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| author | Hirotaka Kato Tomohide Tsukahara Kenji Murata Hiromu Nishikata Yuka Mizue Takashi Sasaya Terufumi Kubo Takayuki Kanaseki Yoshihiko Hirohashi Atsushi Oyagi Tatsuo Maeda Akihiro Miyazaki Toshihiko Torigoe |
| author_facet | Hirotaka Kato Tomohide Tsukahara Kenji Murata Hiromu Nishikata Yuka Mizue Takashi Sasaya Terufumi Kubo Takayuki Kanaseki Yoshihiko Hirohashi Atsushi Oyagi Tatsuo Maeda Akihiro Miyazaki Toshihiko Torigoe |
| author_sort | Hirotaka Kato |
| collection | DOAJ |
| description | Abstract The development of effective immunotherapies for solid tumors remains a significant challenge. In previous studies, we identified PVT1, a long non-coding RNA, with the peptide HF10 derived from PVT1, presented by HLA-A24. This study aims to develop a single-chain variable fragment (scFv) that specifically recognizes the HLA-A24/HF10 complex (HF10 scFv) and to evaluate its specificity, reactivity, and therapeutic potential as part of a T cell engaging bispecific antibody (HF10xCD3) in vitro and in vivo. Using a scFv phage display library, we screened for scFv clones targeting the HLA-A24/HF10 peptide complex. The selected HF10 scFv was engineered into an IgG1 format (HF10-hIgG1), which demonstrated high affinity (KD = 2.18 × 10⁻⁸ M) and specific detection of the HLA-A24/HF10 complex on HLA-A24( +)/PVT1( +) tumor cell lines. Furthermore, HF10 scFv was incorporated into a T cell engaging bispecific antibody (HF10xCD3), which induced cytotoxicity in these tumor cell lines. In a mouse xenograft model, HF10xCD3 administration exhibited significant anti-tumor activity. In conclusion, HF10xCD3 represents a promising candidate for immunotherapy targeting solid tumors. |
| format | Article |
| id | doaj-art-65edf236c6d3473186febd86db5640e5 |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-65edf236c6d3473186febd86db5640e52025-08-20T02:49:23ZengSpringerCancer Immunology, Immunotherapy1432-08512025-03-0174411110.1007/s00262-025-03976-7Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1Hirotaka Kato0Tomohide Tsukahara1Kenji Murata2Hiromu Nishikata3Yuka Mizue4Takashi Sasaya5Terufumi Kubo6Takayuki Kanaseki7Yoshihiko Hirohashi8Atsushi Oyagi9Tatsuo Maeda10Akihiro Miyazaki11Toshihiko Torigoe12Department of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityOncology Clinical Exploratory Research II, Ono Pharmaceutical, Co., Ltd.Research Center of Oncology Group VI, Ono Pharmaceutical, Co., Ltd.Department of Pathology, School of Medicine, Sapporo Medical UniversityDepartment of Pathology, School of Medicine, Sapporo Medical UniversityAbstract The development of effective immunotherapies for solid tumors remains a significant challenge. In previous studies, we identified PVT1, a long non-coding RNA, with the peptide HF10 derived from PVT1, presented by HLA-A24. This study aims to develop a single-chain variable fragment (scFv) that specifically recognizes the HLA-A24/HF10 complex (HF10 scFv) and to evaluate its specificity, reactivity, and therapeutic potential as part of a T cell engaging bispecific antibody (HF10xCD3) in vitro and in vivo. Using a scFv phage display library, we screened for scFv clones targeting the HLA-A24/HF10 peptide complex. The selected HF10 scFv was engineered into an IgG1 format (HF10-hIgG1), which demonstrated high affinity (KD = 2.18 × 10⁻⁸ M) and specific detection of the HLA-A24/HF10 complex on HLA-A24( +)/PVT1( +) tumor cell lines. Furthermore, HF10 scFv was incorporated into a T cell engaging bispecific antibody (HF10xCD3), which induced cytotoxicity in these tumor cell lines. In a mouse xenograft model, HF10xCD3 administration exhibited significant anti-tumor activity. In conclusion, HF10xCD3 represents a promising candidate for immunotherapy targeting solid tumors.https://doi.org/10.1007/s00262-025-03976-7Long non-coding RNAOsteosarcomaCarcinomaHLA-A24CTL epitopePeptide |
| spellingShingle | Hirotaka Kato Tomohide Tsukahara Kenji Murata Hiromu Nishikata Yuka Mizue Takashi Sasaya Terufumi Kubo Takayuki Kanaseki Yoshihiko Hirohashi Atsushi Oyagi Tatsuo Maeda Akihiro Miyazaki Toshihiko Torigoe Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 Cancer Immunology, Immunotherapy Long non-coding RNA Osteosarcoma Carcinoma HLA-A24 CTL epitope Peptide |
| title | Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 |
| title_full | Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 |
| title_fullStr | Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 |
| title_full_unstemmed | Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 |
| title_short | Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1 |
| title_sort | development of a t cell engaging bispecific antibody targeting long non coding rna pvt1 |
| topic | Long non-coding RNA Osteosarcoma Carcinoma HLA-A24 CTL epitope Peptide |
| url | https://doi.org/10.1007/s00262-025-03976-7 |
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