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Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Lymphoma | Primary research

Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells

Authors: Hongxia Wang, Liyan Wang, Yanning Li, Guangqi Li, Xiaochun Zhang, Dan Jiang, Yanting Zhang, Liyuan Liu, Yuankui Chu, Guangxian Xu

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Taking advantage of nanobodies (Nbs) in immunotherapy, we investigated the cytotoxicity of Nb-based chimeric antigen receptor T cells (Nb CAR-T) against lymphoma cells.

Methods

CD19 Nb CAR-T, CD20 Nb CAR-T, and Bispecific Nb CAR-T cells were generated by panning anti-human CD19- and CD20-specific nanobody sequences from a natural Nb-expressing phage display library, integrating Nb genes with a lentiviral cassette that included other CAR elements, and finally transducing T cells that were expanded under an optimization system with the above generated CAR lentivirus. Prepared Nb CAR-T cells were cocultured with tumour cell lines or primary tumour cells for 24 h or 5 days to evaluate their biological function.

Results

The nanobodies that we selected from the natural Nb-expressing phage display library had a high affinity and specificity for CD19 and CD20. CD19 Nb CAR-T, CD20 Nb CAR-T and Bispecific Nb CAR-T cells were successfully constructed, and these Nb CAR-T cells could strongly recognize Burkitt lymphoma cell lines (Raji and Daudi), thereby leading to activation, enhanced proliferation, and specific killing of target cells. Furthermore, similar results were obtained when using patient samples as target cells, with a cytotoxicity of approximately 60%.

Conclusions

Nanobody-based CAR-T cells can kill both tumour cell lines and patient-derived tumour cells in vitro, and Nb-based CAR-T cells may be a promising therapeutic strategy in future immunotherapy.
Appendix
Available only for authorised users
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Metadata
Title
Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells
Authors
Hongxia Wang
Liyan Wang
Yanning Li
Guangqi Li
Xiaochun Zhang
Dan Jiang
Yanting Zhang
Liyuan Liu
Yuankui Chu
Guangxian Xu
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Lymphoma
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02151-z

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