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Title: Rapid production of clinical-grade SARS-CoV-2 specific T cells.
Authors: Leung, Wing
Soh, Teck Guan
Linn, Yeh Ching 
Low, Jenny Guek-Hong 
Loh, Jiashen
Chan, Marieta
Chng, Wee Joo 
Koh, Liang Piu 
Poon, Michelle Li-Mei
Ng, King Pan 
Kuick, Chik Hong
Tan, Thuan Tong 
Tan, Lip Kun 
Seng, Michaela Su-Fern 
Keywords: COVID‐19
T Cells
adoptive cell therapy
Issue Date: Oct-2020
Publisher: Hindawi Limited
Citation: Leung, Wing, Soh, Teck Guan, Linn, Yeh Ching, Low, Jenny Guek-Hong, Loh, Jiashen, Chan, Marieta, Chng, Wee Joo, Koh, Liang Piu, Poon, Michelle Li-Mei, Ng, King Pan, Kuick, Chik Hong, Tan, Thuan Tong, Tan, Lip Kun, Seng, Michaela Su-Fern (2020-10). Rapid production of clinical-grade SARS-CoV-2 specific T cells.. Adv Cell Gene Ther 3 (4) : e101-. ScholarBank@NUS Repository.
Abstract: Objectives: To determine whether the frequencies of SARS-CoV-2-specific T cells are sufficiently high in the blood of convalescent donors and whether it is technically feasible to manufacture clinical-grade products overnight for T-cell therapy and assessment of COVID-19 immunity. Methods: One unit of whole blood or leukapheresis was collected from each donor following standard blood bank practices. The leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereafter, functionally reactive cells were enriched overnight using an automated device capturing IFNγ-secreting cells. Results: From 1 × 109 leukocytes, a median of 0.98 × 106 (range 0.56-2.95) IFNγ + T cells were produced from each of the six donors, suggesting a high frequency of SARS-CoV-2 reactive T cells in their blood, even though only one donor had severe COVID-19 requiring mechanical ventilation whereas the other five donors had minor symptoms. A median of 57% of the enriched T cells were IFNγ+ (range 20%-74%), with preferential enrichment of CD56+ T cells and effector memory T cells. TCRVβ-spectratyping confirmed distinctively tall oligoclonal peaks in final products. With just six donors, the probability that a recipient would share at least one HLA allele with one of the donors is >88% among Caucasian, >95% among Chinese, >97% among Malay, and >99% among Indian populations. Conclusions: High frequencies of rapid antigen-reactive T cells were found in convalescent donors, regardless of severity of COVID-19. The feasibility of clinical-grade production of SARS-CoV-2-specific T cells overnight for therapeutics and diagnostics is revealed.
Source Title: Adv Cell Gene Ther
ISSN: 2573-8461
DOI: 10.1002/acg2.101
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