Successful manufacturing of clinical grade SARS-CoV-2 specific T cells for adoptive T cell therapy

Authors: Wing Leung,1,2 Teck Guan Soh, Yeh Ching Linn, Jenny Guek-Hong Low, Jiashen Loh, Marieta Chan, Wee Joo Chng, Liang Piu Koh, Michelle Li-Mei Poon, King Pan Ng, Chik Hong Kuick, Thuan Tong Tan, Lip Kun Tan, Michaela Su-fern Seng.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.24.20077487v1.full.pdf

Journal/ Pre-Print: MedRxiv

Tags: Immunology/Immunity, T-cell therapy

Research Highlights 

1. This study shows that ex vivo expansion and recovery of IFN-g producing CD4 and CD8 T cells from SARS-CoV-2-convalescent donors can be achieved by the use of peptide libraries comprising the S, M and N viral proteins.

2. Production of 105 to 106 clinical grade, viral-specific effector memory T cells can be achieved. Enrichment of IFN-g secreting CD4 and CD8 T cells with effector memory and central memory phenotype are reported.

3. The authors report oligoclonal enrichment of T cells expressing TCR variable beta sequences 3, 16 and 17.

Summary

Leung et al. applied a functional IFN- γ Cytokine Capture System for fast ex vivo enrichment of SARS-Cov-2 specific effector and central memory CD4+ and CD8+ T cells. Peripheral blood of 2 COVID-19 convalescent, Chinese Singaporean residents was used. Cells were stimulated with a library of overlapping peptides derived from the spike (S), matrix (M) and nucleoprotein (N) of SARS-CoV-2. They report sufficient global T cell frequencies of IFN-g secreting virus-specific T cells for potential therapy and fast COVID-19 diagnosis. Sharing of at least one of their HLA allomorphs was reported with >30% of the general Chinese population.

Impact for SARS-CoV2/COVID19 research efforts

Provides evidence that an antiviral IFN-g producing and oligoclonal cellular immune response is generated in SARS-Cov-2 convalescent donors. The authors suggest that this should be considered for T cell therapy.

Study Type

· Ex vivo/Clinical Samples Study (Recovered COVID-19 patient samples)

Strengths and limitations of the paper

Novelty: Demonstration of TH1-like T-cell immunity to SARS-CoV-2 S, N and M proteins in convalescent donors, frequent enough to be considered in adoptive T-cell therapies in a Singapore-Chinese population.

Standing in the field: Not known

Appropriate statistics: No

Viral model used: none.

Translatability: Potential use for T-cell therapies but more research required to establish safety and efficacy. No protection studies performed with recipient donors or in vitro to demonstrate functionality of CD8+ or CD4+ T cells.

Main limitations: Data collected from two donors and a Singapore-Chinese population. No Healthy donors as controls. Limited phenotype of cells. Analyses of donors with different MHC alleles would be necessary to evaluate its potential use as a more widely applicable adoptive T cell therapy. The risk of GVHD is deemed to be low but this needs verification.