Rapid production of clinical‐grade SARS‐CoV‐2 specific T cells

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 × 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. TCRVβspectratyping 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.

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy

“…Given the vast number of convalescent donors, finding the proper haploidentical donor based on HLA typing would not be difficult. Based on previously published data ( Leung et al, 2020 ), this donor can cover around 93.6% of Spain’s population. In accordance with the HLA donor-recipient match, we estimate that four donors will cover almost the whole of Spain’s population ( Leen et al, 2013 ; Leung et al, 2020 ).…”

“…Based on previously published data ( Leung et al, 2020 ), this donor can cover around 93.6% of Spain’s population. In accordance with the HLA donor-recipient match, we estimate that four donors will cover almost the whole of Spain’s population ( Leen et al, 2013 ; Leung et al, 2020 ). These cells are expected to remain in the patients until the host immune system is recovered.…”

“…The role of adaptive immunity in COVID-19 and the protective immunity conferred by T cells is still being characterized ( Grifoni et al, 2020 ; Huang et al, 2020 ; Leung et al, 2020 ; Rodda et al, 2020 ; Sekine et al, 2020 ), and the role of memory T cells in conferring protection against SARS-CoV-2 has not yet been properly defined. The presence of memory T cells specific for another SARS coronavirus was found up to 11 years post-infection ( Ng et al, 2016 ).…”

Rapid GMP-Compliant Expansion of SARS-CoV-2–Specific T Cells From Convalescent Donors for Use as an Allogeneic Cell Therapy for COVID-19

“…A VST product based on this manufacturing method, or others currently in development (42), will require careful First in Human clinical trials to determine the best route for use of VST in SARS-CoV-2 infection. Patients treated with VSTs for CMV-or Epstein-Barr Virus (EBV)-mediated disease are commonly immunesuppressed as a result of the treatment pathway for stem cell or solid organ transplantation (19)(20)(21).…”

Overview of Cellular Immunotherapies within Transfusion Medicine for the Treatment of Malignant Diseases

“…They can be found under identifier numbers NCT04457726 (Singapore), NCT04762186 (Germany), and NCT04401410 (Houston, TX, USA), to name just a few. The generation of SARS-CoV-2-specific T cells was demonstrated to be feasible using automatic enrichment devices, such as CliniMACS Prodigy ® [ 64 ]. Furthermore, the increasing number of convalescent patients will facilitate donor recruitment in the future.…”