期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00462-1
关键词
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资金
- Project of National Natural Scientific Foundation of China [81773254]
- Programs for Changjiang Scholars and Innovative Research Team in University [IRT_15R13]
- International Cooperation Project of the Misnistry of Science and Technology of China [2015DFA31320]
- Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA139001]
- Project for International Nanobody Research Center of Guangxi [GuiKe-AD17195001]
- NIH-NIEHS (RIVER Award) [R35 ES030443-01]
- NIEHS Superfund Research Program [P42 ES004699]
- Guangxi First-class Discipline Project for Pharmaceutical Sciences [GXFCDP-PS-2018]
- National Key Research and Development Plan Intergovernmental Cooperation in International Scientific and Technological Innovation [2019YFE0117300]
- Guangxi Science and Technology Base and Talents Project [GuiKe-AD20238062]
The development of nanobody-based CAR-T cells targeting CD105 antigen has shown promising results in vitro and in vivo, exhibiting specific anti-cancer effects against solid tumors. This strategy has the potential to be an effective treatment for solid tumors by utilizing CRISPR/Cas9 technology to engineer CAR-T cells.
Chimeric antigen receptor-based T-cell immunotherapy is a promising strategy for treatment of hematological malignant tumors; however, its efficacy towards solid cancer remains challenging. We therefore focused on developing nanobody-based CAR-T cells that treat the solid tumor. CD105 expression is upregulated on neoangiogenic endothelial and cancer cells. CD105 has been developed as a drug target. Here we show the generation of a CD105-specific nanobody, an anti-human CD105 CAR-T cells, by inserting the sequences for anti-CD105 nanobody-linked standard cassette genes into AAVS1 site using CRISPR/Cas9 technology. Co-culture with CD105(+) target cells led to the activation of anti-CD105 CAR-T cells that displayed the typically activated cytotoxic T-cell characters, ability to proliferate, the production of pro-inflammatory cytokines, and the specific killing efficacy against CD105(+) target cells in vitro. The in vivo treatment with anti-CD105 CAR-T cells significantly inhibited the growth of implanted CD105(+) tumors, reduced tumor weight, and prolonged the survival time of tumor-bearing NOD/SCID mice. Nanobody-based CAR-T cells can therefore function as an antitumor agent in human tumor xenograft models. Our findings determined that the strategy of nanobody-based CAR-T cells engineered by CRISPR/Cas9 system has a certain potential to treat solid tumor through targeting CD105 antigen.
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