Rapid production of clinical-grade SARS-CoV-2 specific T cells.

Autor:	Leung W; Department of Haematology/Oncology KK Women's and Children's Hospital SingHealth Singapore.; Duke-NUS Medical School Singapore., Soh TG; Department of Haematology-Oncology National University Hospital Singapore., Linn YC; Duke-NUS Medical School Singapore.; Department of Haematology Singapore General Hospital Singapore., Low JG; Duke-NUS Medical School Singapore.; Department of Infectious Diseases Singapore General Hospital Singapore., Loh J; Department of Infectious Disease Sengkang General Hospital Singapore., Chan M; Blood Services Group Health Sciences Authority Singapore., Chng WJ; Department of Haematology-Oncology National University Hospital Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore., Koh LP; Department of Haematology-Oncology National University Hospital Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore., Poon ML; Department of Haematology-Oncology National University Hospital Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore., Ng KP; Department of Haematology/Oncology KK Women's and Children's Hospital SingHealth Singapore., Kuick CH; Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital SingHealth Singapore., Tan TT; Duke-NUS Medical School Singapore.; Department of Infectious Diseases Singapore General Hospital Singapore., Tan LK; Department of Haematology-Oncology National University Hospital Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore., Seng MS; Department of Haematology/Oncology KK Women's and Children's Hospital SingHealth Singapore.; Duke-NUS Medical School Singapore.
Jazyk:	angličtina
Zdroj:	Advances in cell and gene therapy [Adv Cell Gene Ther] 2020 Oct; Vol. 3 (4), pp. e101. Date of Electronic Publication: 2020 Jul 31.
DOI:	10.1002/acg2.101
Abstrakt:	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 × 10 9 leukocytes, a median of 0.98 × 10 6 (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. Competing Interests: WL is a part‐time advisor to Miltenyi Biomedicine. (© 2020 The Authors. Advances in Cell and Gene Therapy published by John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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