4.7 Article

Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy

Journal

Publisher

SPRINGERNATURE
DOI: 10.1038/s41392-021-00462-1

Keywords

-

Funding

  1. Project of National Natural Scientific Foundation of China [81773254]
  2. Programs for Changjiang Scholars and Innovative Research Team in University [IRT_15R13]
  3. International Cooperation Project of the Misnistry of Science and Technology of China [2015DFA31320]
  4. Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA139001]
  5. Project for International Nanobody Research Center of Guangxi [GuiKe-AD17195001]
  6. NIH-NIEHS (RIVER Award) [R35 ES030443-01]
  7. NIEHS Superfund Research Program [P42 ES004699]
  8. Guangxi First-class Discipline Project for Pharmaceutical Sciences [GXFCDP-PS-2018]
  9. National Key Research and Development Plan Intergovernmental Cooperation in International Scientific and Technological Innovation [2019YFE0117300]
  10. Guangxi Science and Technology Base and Talents Project [GuiKe-AD20238062]

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available