Hematopoietic lineage-converted T cells carrying tumor-associated antigen-recognizing TCRs effectively kill tumor cells

Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells....

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Bibliographic Details
Published in:Journal for immunotherapy of cancer 2020-07, Vol.8 (2), p.e000498
Main Authors: Hu, Fangxiao, Huang, Dehao, Luo, Yuxuan, Zhou, Peiqing, Lv, Cui, Wang, Kaitao, Weng, Qitong, Liu, Xiaofei, Guan, Yuxian, Geng, Yang, Du, Juan, Chen, Jiekai, Wang, Jinyong, Wu, Hongling
Format: Article
Language:English
Subjects:
Antigens
Basic tumor immunology
Bone marrow
Cancer
Immunotherapy
Lymphocytes
Melanoma
Short Report
Stem cells
T lymphocytes
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Summary:Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells. We previously reported that enforced expression of Hoxb5 converted B cells into induced T (iT) cells in vivo. Here, we successfully regenerated naive OT1 (major histocompatibility complex I restricted ovalbumin antigen) iT cells (OT1-iT) in vivo by expressing Hoxb5 in pro-pre-B cells in the OT1 transgenic mouse. The OT1-iT cells can be activated and expanded in vitro in the presence of tumor cells. Particularly, these regenerated OT1-iT cells effectively eradicated tumor cells expressing the TAA (ovalbumin) both in vitro and in vivo. This study provides insights into the translational applications of blood lineage-transdifferentiated T cells in immunotherapy.
ISSN:2051-1426
2051-1426
DOI:10.1136/jitc-2019-000498