Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy
SUMMARY Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Basar, Rafet [VerfasserIn] |
|---|
| Links: |
|---|
| doi: |
10.1101/2020.09.15.298547 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI018797881 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI018797881 | ||
| 003 | DE-627 | ||
| 005 | 20230429094354.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200924s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.09.15.298547 |2 doi | |
| 035 | |a (DE-627)XBI018797881 | ||
| 035 | |a (biorXiv)10.1101/2020.09.15.298547 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Basar, Rafet |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a SUMMARY Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing. | ||
| 700 | 1 | |a Uprety, Nadima |e verfasserin |4 aut | |
| 700 | 1 | |a Ensley, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Daher, May |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, Kimberly |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Aung, Fleur |e verfasserin |4 aut | |
| 700 | 1 | |a Shanley, Mayra |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Bingqian |e verfasserin |4 aut | |
| 700 | 1 | |a Gokdemir, Elif |e verfasserin |4 aut | |
| 700 | 1 | |a Mendt, Mayela |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, Francia Reyes |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Sunil |e verfasserin |4 aut | |
| 700 | 1 | |a Laskowski, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Muniz-Feliciano, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Banerjee, Pinaki |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Sufang |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia, Luciana Melo |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Shaim, Hila |e verfasserin |4 aut | |
| 700 | 1 | |a Yates, Sean G. |e verfasserin |4 aut | |
| 700 | 1 | |a Marin, David |e verfasserin |4 aut | |
| 700 | 1 | |a Kaur, Indreshpal |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Sheetal |e verfasserin |4 aut | |
| 700 | 1 | |a Mak, Duncan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Angelique |e verfasserin |4 aut | |
| 700 | 1 | |a Miao, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Dou, Jinzhuang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Champlin, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Shpall, Elizabeth J. |e verfasserin |4 aut | |
| 700 | 1 | |a Rezvani, Katayoun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2021) vom: 15. Dez. |
| 773 | 1 | 8 | |g year:2021 |g day:15 |g month:12 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.celrep.2021.109432 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.09.15.298547 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2021 |b 15 |c 12 | ||
| 953 | |2 045F |a 570 | ||