頁籤選單縮合
題 名 | A Non-genetic Engineering Platform for Rapidly Generating and Expanding Cancer-specific Armed T Cells |
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作 者 | Chen, Yi-jou; Chen, Michael; Cheng, Tian-lu; Tsai, Yi-shan; Wang, Chang-hung; Chen, Che-yi; Wu, Tung-yun; Tzou, Shey-cherng; Wang, Kai-hung; Cheng, Jing-jy; Kao, An-pei; Lin, Shyr-yi; Chuang, Kuo-hsiang; | 書刊名 | Journal of Biomedical Science |
卷 期 | 30 2023[民112] |
頁 次 | 頁(35)1-(35)19 |
分類號 | 368.5 |
關鍵詞 | Adoptive T cell therapy; Cancer‑specific T cell; Bispecific antibody; BsAb; Virus‑free engineering platform; BsAb‑armed T cell; |
語 文 | 英文(English) |
DOI | 10.1186/s12929-023-00929-z |
英文摘要 | Background Cancer‑specific adoptive T cell therapy has achieved successful milestones in multiple clinical treat‑ ments. However, the commercial production of cancer‑specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus‑based gene transfection, or insufficient T cell purity. Methods In this study, we developed a non‑genetic engineering technology for rapidly manufacturing a large amount of cancer‑specific T cells by utilizing a unique anti‑cancer/anti‑CD3 bispecific antibody (BsAb) to directly cul‑ ture human peripheral blood mononuclear cells (PBMCs). The anti‑CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti‑cancer moiety of the BsAb provided these BsAb‑armed T cells with the cancer‑targeting ability, which transformed the naïve T cells into cancer‑specific BsAb‑armed T cells. Results With this technology, a large amount of cancer‑specific BsAb‑armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb‑armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF‑α and IFN‑γ) were dramatically released from the BsAb‑armed T cells after engaging cancer cells, resulting in a remarkable anti‑cancer efficacy. Notably, the BsAb‑ armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors. Conclusions Collectively, the BsAb‑armed T cell technology represents a simple, time‑saving, and highly safe method to generate highly pure cancer‑specific effector T cells, thereby providing an affordable T cell immunotherapy to patients. |
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