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Transpl Infect Dis . Adoptive transfer of ex-vivo expanded SARS-CoV-2-specific Cytotoxic Lymphocytes: a viable strategy for COVID-19 immunosuppresse

tetano

Editor, Senior Moderator
Transpl Infect Dis


. 2021 Mar 17;e13602.
doi: 10.1111/tid.13602. Online ahead of print.
Adoptive transfer of ex-vivo expanded SARS-CoV-2-specific Cytotoxic Lymphocytes: a viable strategy for COVID-19 immunosuppressed patients?


Manuel Guerreiro[SUP] 1 2 [/SUP], Crist?bal Aguilar-Gallardo[SUP] 1 2 [/SUP], Juan Montoro[SUP] 1 2 [/SUP], Clara Franc?s-G?mez[SUP] 3 [/SUP], V?ctor Latorre[SUP] 3 [/SUP], Irene Luna[SUP] 1 [/SUP], Dolores Planelles[SUP] 4 5 [/SUP], Mar?a Paz Carrasco[SUP] 5 [/SUP], Mar?a Dolores G?mez[SUP] 6 [/SUP], Eva Mar?a Gonz?lez-Barber?[SUP] 6 [/SUP], Cristina Aguado[SUP] 7 [/SUP], Amparo Sempere[SUP] 1 8 [/SUP], Pilar Solves[SUP] 1 [/SUP], In?s G?mez-Segu?[SUP] 1 [/SUP], Aitana Balaguer-Rosello[SUP] 1 2 [/SUP], Alberto Louro[SUP] 2 [/SUP], Aurora Perla[SUP] 1 [/SUP], Luis Larrea[SUP] 4 5 [/SUP], Jaime Sanz[SUP] 1 8 [/SUP], Cristina Arbona[SUP] 4 5 [/SUP], Javier de la Rubia[SUP] 1 [/SUP], Ron Geller[SUP] 3 [/SUP], Miguel ?ngel Sanz[SUP] 2 [/SUP], Guillermo Sanz[SUP] 1 8 [/SUP], Jos? Luis Pi?ana[SUP] 1 8 9 [/SUP]



Affiliations

Abstract

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in 3 different donors' scenarios: 1) SARS-CoV-2 asymptomatic infection/negative serology, 2) SARS-CoV-2 symptomatic infection/positive serology and 3) no history of SARS-CoV-2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3+ cells (80.3% and 62.7%, respectively) with CD4+ dominance (60% in both donors). Higher numbers of VST were obtained from the donor 2 as compared to donor 1. T-cell clonality test showed oligoclonal reproducible peaks on a polyclonal background for both donors. In contrast, VST could be neither expanded nor primed in a donor without evidence of prior infection. This proof-of-concept study supports the feasibility of expanding ex vivo SARS-CoV-2-specific VST from blood of convalescent donors. The results raise the question of whether the selection of seropositive donors may be a strategy to obtain cell lines enriched in their SARS-CoV-2-specificity for future adoptive transfer to immunosuppressed patients.

Keywords: Adoptive immunotherapy; COVID-19; SARS-CoV-2; Third-party donors; Virus-specific T cells; lymphocyte expansion; respiratory virus.
 
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