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Blood
. 2020 Dec 17;136(25):2905-2917.
doi: 10.1182/blood.2020008488.
SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein
Michael D Keller 1 2 3 , Katherine M Harris 1 , Mariah A Jensen-Wachspress 1 , Vaishnavi V Kankate 1 , Haili Lang 1 , Christopher A Lazarski 1 , Jessica Durkee-Shock 1 4 , Ping-Hsien Lee 1 , Kajal Chaudhry 1 , Kathleen Webber 1 , Anushree Datar 1 , Madeline Terpilowski 1 , Emily K Reynolds 1 , Eva M Stevenson 5 , Stephanie Val 1 , Zoe Shancer 1 , Nan Zhang 1 , Robert Ulrey 1 , Uduak Ekanem 1 , Maja Stanojevic 1 , Ashley Geiger 1 , Hua Liang 6 , Fahmida Hoq 1 , Allistair A Abraham 1 3 7 , Patrick J Hanley 1 3 7 , C Russell Cruz 1 3 , Kathleen Ferrer 8 , Lesia Dropulic 9 , Krista Gangler 10 , Peter D Burbelo 11 , R Brad Jones 5 , Jeffrey I Cohen 9 , Catherine M Bollard 1 3 7
Affiliations
- PMID: 33331927
- DOI: 10.1182/blood.2020008488
Abstract
T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2-specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.