학술논문
Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE)
Document Type
article
Author
A. Pérez-Martínez; M. Mora-Rillo; C. Ferreras; P. Guerra-García; B. Pascual-Miguel; C. Mestre-Durán; A.M. Borobia; A.J. Carcas; J. Queiruga-Parada; I. García; E. Sánchez-Zapardiel; M. Gasior; R. De Paz; A. Marcos; J.L. Vicario; A. Balas; M.A. Moreno; C. Eguizabal; C. Solano; J.R. Arribas; R.de Miguel Buckley; R. Montejano; B. Soria
Source
EClinicalMedicine, Vol 39, Iss , Pp 101086- (2021)
Subject
Language
English
ISSN
2589-5370
Abstract
Background: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. Methods: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA− memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA− memory T cells. Clinicaltrials.gov registration: NCT04578210. Findings: All participants’ clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. Interpretation: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA− memory T cells is feasible and safe. Funding: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.