A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect

Chimeric antigen receptor T cells (CAR-T cells) targeting of CD19 antigen has been proven to be effective and successful in B cell acute lymphoblastic leukemia. The traditional CAR delivery systems have several problems such as poor biosafety, low loading capacity, and low transfection efficiency. U...

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Bibliographic Details
Published in:RSC advances 2018-01, Vol.8 (27), p.14975-14982
Main Authors: Fan, Jing, He, Qianjun, Jin, Zhaokui, Chen, Wei, Huang, Weiren
Format: Article
Language:English
Subjects:
Addition polymerization
Anticancer properties
Antigens
Cationic polymerization
Chemical reactions
Chemical synthesis
Chemistry
Deoxyribonucleic acid
DNA
Interferon
Interleukins
Lymphocytes
MPEG encoders
Plasmids
Polyethylene glycol
Polyethyleneimine
Polymers
Self-assembly
T cell receptors
Video compression
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Summary:Chimeric antigen receptor T cells (CAR-T cells) targeting of CD19 antigen has been proven to be effective and successful in B cell acute lymphoblastic leukemia. The traditional CAR delivery systems have several problems such as poor biosafety, low loading capacity, and low transfection efficiency. Utilization of nanocarriers for CAR delivery offers new possibilities for CAR-T treatment. In the present study, an anti-CD19 CAR expression lentivirus plasmid was constructed for CAR delivery and immunotherapy. In addition, a three-segment amphiphilic co-polymer, methoxy polyethylene glycol-branched polyethyleneimine-poly(2-ethylbutyl phospholane) (mPEG-bPEI-PEBP) was synthesized via click reaction as the carrier with cationic PEI, capable of delivering the CAR and packaging plasmids to co-transfect Jurkat cells and undergo expression. The PEBP and mPEG parts of the co-polymer provide hydrophobic and hydrophilic interfaces and lead to the co-polymer self-assembly into micelles in water and encapsulation of the DNA plasmids. The mPEG-bPEI-PEBP-DNA composites with different N/P ratios were incubated with the CD19 overexpression K562 cells to identify the CAR functions. The obtained CAR-Jurkat cells had the ability to secrete interferon-γ and interleukin-2. The cytotoxic effects to CD19-K562 cells suggest that the induced CAR-Jurkat cells have an excellent targeted antitumor activity. A three-segment amphiphilic co-polymer mPEG-bPEI-PEBP was synthesized as the nanocarrier with cationic PEI, capable of delivering the CAR and packaging plasmids into Jurkat cells to generate the CAR-T cells for anti-CD19 immunotherapy study.
ISSN:2046-2069
2046-2069
DOI:10.1039/c8ra02133c