Academic Journal
Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor
| العنوان: | Development of T cell receptor‐engineered T cells targeting the sarcoma‐associated antigen papillomavirus binding factor |
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| المؤلفون: | Hamada, Shuto, Tsukahara, Tomohide, Watanabe, Yuto, Murata, Kenji, Mizue, Yuka, Kubo, Terufumi, Kanaseki, Takayuki, Hirohashi, Yoshihiko, Emori, Makoto, Nakatsugawa, Munehide, Teramoto, Atsushi, Yamashita, Toshihiko, Torigoe, Toshihiko |
| المساهمون: | Japan Society for the Promotion of Science, Princess Takamatsu Cancer Research Fund |
| المصدر: | Cancer Science ; volume 115, issue 1, page 24-35 ; ISSN 1347-9032 1349-7006 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | We previously identified papillomavirus binding factor (PBF) as an osteosarcoma antigen recognized by an autologous cytotoxic T lymphocyte clone. Vaccination with PBF‐derived peptide presented by HLA‐A24 (PBF peptide) elicited strong immune responses. In the present study, we generated T cell receptor‐engineered T cells (TCR‐T cells) directed against the PBF peptide (PBF TCR‐T cells). PBF TCR was successfully transduced into T cells and detected using HLA‐A*24:02/PBF peptide tetramer. PBF TCR‐T cells generated from a healthy donor were highly expanded and recognized T2‐A24 cells pulsed with PBF peptide, HLA‐A24 + 293T cells transfected with PBF cDNA, and sarcoma cell lines. To establish an adoptive cell therapy model, we modified the PBF TCR by replacing both α and β constant regions with those of mice (hybrid PBF TCR). Hybrid PBF TCR‐T cells also showed reactivity against T2‐A24 cells pulsed with PBF peptide and to HLA‐A24 + 293T cells transfected with various lengths of PBF cDNA including the PBF peptide sequence. Subsequently, we generated target cell lines highly expressing PBF (MFH03‐PBF [short] epitope [+]) containing PBF peptide with in vivo tumorigenicity. Hybrid PBF TCR‐T cells exhibited antitumor effects compared with mock T cells in NSG mice xenografted with MFH03‐PBF (short) epitope (+) cells. CD45 + T cells significantly infiltrated xenografted tumors only in the hybrid PBF TCR T cell group and most of these cells were CD8‐positive. CD8 + T cells also showed Ki‐67 expression and surrounded the CD8‐negative tumor cells expressing Ki‐67. These findings suggest that PBF TCR‐T cell therapy might be a candidate immunotherapy for sarcoma highly expressing PBF. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/cas.15967 |
| الاتاحة: | http://dx.doi.org/10.1111/cas.15967 https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.15967 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.64B09E1A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/cas.15967 |
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