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

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

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.