- 作者: Yi-Jou Chen, Michael Chen, Tian-Lu Cheng, Yi-Shan Tsai, Chang-Hung Wang, Che-Yi Chen, Tung-Yun Wu, Shey-Cherng Tzou, Kai-Hung Wang, Jing-Jy Cheng, An-Pei Kao, Shyr-Yi Lin & Kuo-Hsiang Chuang
- 作者服務機構: 1.Center for Reproductive Medicine, Kuo General Hospital, Tainan, Taiwan 2.CytoArm Co., Ltd, Taipei, Taiwan 3.Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan 4.Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 5.Departmet of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan 6.Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei, Taiwan 7.Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan 8.Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 9.Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan 10.Master Program in Clinical Genomics and Proteomics, Taipei Medical University, Taipei, Taiwan 11.National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan 12.Ph.D Program in Biotechnology Research and Development, Taipei Medical University, Taipei, Taiwan 13.Ph.D. Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan 14.The Ph.D. Program of Translational Medicine, Taipei Medical University, Taipei, Taiwan 15.TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan 16.Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Background Cancer-specifc adoptive T cell therapy has achieved successful milestones in multiple clinical treat‑
ments. However, the commercial production of cancer-specifc T cells is often hampered by laborious cell culture
procedures, the concern of retrovirus-based gene transfection, or insufcient T cell purity.
Methods In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large
amount of cancer-specifc T cells by utilizing a unique anti-cancer/anti-CD3 bispecifc 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 diferentiation 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-specifc
BsAb-armed T cells.
Results With this technology, a large amount of cancer-specifc BsAb-armed T cells can be rapidly generated with
a purity of over 90% in 7 days. These BsAb-armed T cells efciently 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 efcacy. Notably, the BsAbarmed 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-specifc efector T cells, thereby providing an afordable T cell immunotherapy
to patients. - 中文關鍵字:
- 英文關鍵字: Adoptive T cell therapy, Cancer-specifc T cell, Bispecifc antibody (BsAb), Virus-free engineering platform, BsAb-armed T cell