Abstract
Background aims
Third party virus-specific T cells (VST) has shown efficacy for opportunistic virus
infection which do not have effective treatment or are drug-refractory. We describe
our preparatory work in setting up a third-party VST bank for a multi-ethnic Asian
population.
Methods
Discarded white cells from regular blood bank plateletpheresis donors with known locally
prevalent HLA antigens were cultured in small scale to generate VST against Adenovirus,
BK virus, Cytomegalovirus, Epstein–Barr virus, and Human Herpes Virus 6. Multi-virus
specific T cells (multi-VST) were also generated against all 5 viruses in single cultures.
A strategy of allelic typing for donors with good and broad-spectrum cytotoxicity
together with consideration on HLA restriction for the virus epitope was used to select
combinations of VST lines for a hypothetical third party VST bank. The breadth of
coverage based on these selection criteria was validated using our database of 100
post haematopoietic stem cell transplant patients.
Results
We show that 50%, 42%, 56%, 56% and 42% of single VST cultures demonstrated specific
cytotoxicity against AdV, BKV, CMV, EBV and HHV6 respectively. Twenty four of the
36 multi-VST lines showed activity against at least 2 of the 5 viruses studied. A
carefully selected combination of just 6 VST lines can offer VST with at least 1 allelic
match to 99% of potential recipients, while 92% can find 2 allelic matches and 79%
can find 3 allelic matches.
Conclusions
This preparatory work confirms that a cost-effective strategy recruiting a small number
of pre-characterized donors can generate VST lines with broad coverage for a multi-ethnic
Asian patient population, thereby laying the foundation for setting up of a third
party VST bank for Asian patients.
Key Words
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Article info
Publication history
Published online: March 06, 2023
Accepted:
February 4,
2023
Received:
September 26,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.