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A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells

Authors :
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
Source :
Journal of Biomedical Science, Vol 30, Iss 1, Pp 1-19 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Background Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. 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 culture 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.

Details

Language :
English
ISSN :
14230127
Volume :
30
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Biomedical Science
Publication Type :
Academic Journal
Accession number :
edsdoj.3306fd61a6ee4e49b2484aa0cb693348
Document Type :
article
Full Text :
https://doi.org/10.1186/s12929-023-00929-z