Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19

  1. Rachel S Cooper
  2. Alasdair R Fraser
  3. Linda Smith
  4. Paul Burgoyne
  5. Stuart N Imlach
  6. Lisa M Jarvis
  7. Sharon Zahra
  8. Marc L. Turner
  9. John DM Campbell

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Abstract

COVID-19 disease caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. Here we show that SARS-CoV-2-exposed blood donations contain CD4 and CD8 memory T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These peptides can be used to isolate virus-specific T cells in a GMP-compliant process. These T cells can be rapidly expanded using GMP-compliant reagents for use as a therapeutic product. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 10 10 to 10 11 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for treatment of COVID-19 patients

One Sentence Summary

CD4+ and CD8+ T cells specific for SARS-CoV-2 can be isolated from convalescent donors and rapidly expanded to therapeutic doses at GMP standard, maintaining the desired central memory phenotype required for protective immune responses against severe COVID-19 infections.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.05.237867: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Flow Cytometry Data Analysis: Analysis of all flow cytometry data was performed using either MACSQuantify (Miltenyi Biotec) for cell counts, or FlowJo version 7 (TreeStar Inc) for wider phenotyping analysis.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical Analysis: Statistical analysis was performed using GraphPad Prism version 8.4.2 (GraphPad Software).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of this study: This study has used the 3 SARS-CoV-2 Ag peptide pools available from April 2020 to generate the phenotyping and expansion data of antigen-specific T cells. Additional antigens may reveal a fuller picture of the immune response in COVID-19, although their addition to the T cell expansion method described here could have a positive additive effect. The demographics of the local donor pool used is necessarily limited to blood donors who have undergone mild COVID-19 disease. Different T cell responses and proliferation characteristics may be found in other donor populations recovering from a range of COVID-19 symptoms. Clinical use of this product will require controlled clinical trials for safety and efficacy assessment.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 33, 34, 37, 27, 29 and 31. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.08.05.237867 on bioRxiv