Abstract
Background aims
Most current chimeric antigen receptor (CAR) T cells are generated by viral transduction,
which induces persistent expression of CARs and may cause serious undesirable effects.
Messenger RNA (mRNA)-based approaches in manufacturing CAR T cells are being developed
to overcome these challenges. However, the most common method of delivering mRNA to
T cells is electroporation, which can be toxic to cells.
Methods
The authors designed and engineered an exosome delivery platform using the bacteriophage
MS2 system in combination with the highly expressed protein lysosome-associated membrane
protein 2 isoform B on exosomes.
Results
The authors’ delivery platform achieved specific loading and delivery of mRNA into
target cells and achieved expression of specific proteins, and anti-CD3/CD28 single-chain
variable fragments (scFvs) expressed outside the exosomal membrane effectively activated
primary T cells in a similar way to commercial magnetic beads.
Conclusions
The delivery of CAR mRNA and anti-CD3/CD28 scFvs via designed exosomes can be used
for ex vivo production of CAR T cells with cancer cell killing capacity. The authors’ results
indicate the potential applications of the engineered exosome delivery platform for
direct conversion of primary T cells to CAR T cells while providing a novel strategy
for producing CAR T cells in vivo.
Key Words
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Article info
Publication history
Published online: February 22, 2023
Accepted:
January 10,
2023
Received:
September 22,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
