PMID- 34405140
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220425
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 39
DP  - 2021 Sep
TI  - 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).
PG  - 101086
LID - 10.1016/j.eclinm.2021.101086 [doi]
LID - 101086
AB  - 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 x 10(5) cells/kg), the next 
      three received the intermediate dose (5 x 10(5) cells/kg) and the last three 
      received the highest dose (1 x 10(6) 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 Innovacion 
      Grant AVI-GVA COVID-19-68 to BS.
CI  - (c) 2021 The Author(s).
FAU - Perez-Martinez, A
AU  - Perez-Martinez A
AD  - Pediatric Hemato-oncology Department, University Hospital La Paz, Madrid, Spain.
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Faculty of Medicine Universidad Autonoma de Madrid, Madrid, Spain.
FAU - Mora-Rillo, M
AU  - Mora-Rillo M
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Infectious Diseases Unit, Internal Medicine Department, University Hospital La 
      Paz, Hospital, Spain.
FAU - Ferreras, C
AU  - Ferreras C
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
FAU - Guerra-Garcia, P
AU  - Guerra-Garcia P
AD  - Pediatric Hemato-oncology Department, University Hospital La Paz, Madrid, Spain.
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Clinical Pharmacology Department University Hospital La Paz, Madrid, Spain.
FAU - Pascual-Miguel, B
AU  - Pascual-Miguel B
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
FAU - Mestre-Duran, C
AU  - Mestre-Duran C
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
FAU - Borobia, A M
AU  - Borobia AM
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Faculty of Medicine Universidad Autonoma de Madrid, Madrid, Spain.
AD  - Clinical Pharmacology Department University Hospital La Paz, Madrid, Spain.
FAU - Carcas, A J
AU  - Carcas AJ
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Faculty of Medicine Universidad Autonoma de Madrid, Madrid, Spain.
AD  - Clinical Pharmacology Department University Hospital La Paz, Madrid, Spain.
FAU - Queiruga-Parada, J
AU  - Queiruga-Parada J
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Clinical Pharmacology Department University Hospital La Paz, Madrid, Spain.
FAU - Garcia, I
AU  - Garcia I
AD  - Clinical Pharmacology Department University Hospital La Paz, Madrid, Spain.
FAU - Sanchez-Zapardiel, E
AU  - Sanchez-Zapardiel E
AD  - Immunology Department, University Hospital La Paz, Madrid, Spain.
FAU - Gasior, M
AU  - Gasior M
AD  - Cell Therapy Unit, Hematology Department, University Hospital La Paz, Madrid, 
      Spain.
FAU - De Paz, R
AU  - De Paz R
AD  - Cell Therapy Unit, Hematology Department, University Hospital La Paz, Madrid, 
      Spain.
FAU - Marcos, A
AU  - Marcos A
AD  - Cell Therapy Unit, Hematology Department, University Hospital La Paz, Madrid, 
      Spain.
FAU - Vicario, J L
AU  - Vicario JL
AD  - Histocompatibility. Centro de Transfusion de Madrid. Madrid, Spain.
FAU - Balas, A
AU  - Balas A
AD  - Histocompatibility. Centro de Transfusion de Madrid. Madrid, Spain.
FAU - Moreno, M A
AU  - Moreno MA
AD  - Histocompatibility. Centro de Transfusion de Madrid. Madrid, Spain.
FAU - Eguizabal, C
AU  - Eguizabal C
AD  - Research Unit, Basque Centre for Blood Transfusion and Human Tissues, Osakidetza, 
      Galdakao, Bizkaia, Spain.
AD  - Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research 
      Institute, Barakaldo, Bizkaia, Spain.
FAU - Solano, C
AU  - Solano C
AD  - INCLIVA, Hospital Clinico Universitario de Valencia. Health Research Institute, 
      University of Valencia, Spain.
FAU - Arribas, J R
AU  - Arribas JR
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Infectious Diseases Unit, Internal Medicine Department, University Hospital La 
      Paz, Hospital, Spain.
FAU - Buckley, R de Miguel
AU  - Buckley RM
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Infectious Diseases Unit, Internal Medicine Department, University Hospital La 
      Paz, Hospital, Spain.
FAU - Montejano, R
AU  - Montejano R
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, University Hospital La 
      Paz, Madrid, Spain.
AD  - Infectious Diseases Unit, Internal Medicine Department, University Hospital La 
      Paz, Hospital, Spain.
FAU - Soria, B
AU  - Soria B
AD  - Institute of Bioengineering, Miguel Hernandez University, Elche, Alicante, Spain.
AD  - Health Research Institute- ISABIAL, Alicante University Hospital, Alicante, 
      Spain.
AD  - University Pablo de Olavide, Sevilla, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT04578210
PT  - Journal Article
DEP - 20210813
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC8361305
COIS- AP-M filed patent EP20382850 on Memory T cells as adoptive cell therapy for viral 
      diseases. CF filed patent EP20382850 on Memory T cells as adoptive cell therapy 
      for viral diseases. BS received salary from University Miguel Hernandez, a grant 
      from Agencia Valenciana de Innovacion, support from Al-Andalus Biopharma and 
      medical writing from Comunidad de Madrid, since the initial planning of the work. 
      He received grant AVI-GVA CO19-068 and consulting fees from Gilead-Weber. BS is 
      on the board at Institut de Bioengineria de Catalunya and Laminar 
      Pharmaceuticals. BS filed patent EP20382850 on Memory T cells as adoptive cell 
      therapy for viral diseases. BS reports an unpaid role with FAID. BS reports the 
      receipt of equipment, materials, drugs, medical writing, gifts or other services 
      from Al-Andalus BioPharmaSL. CS received fees from MSD, Pfizer and Gilead not 
      related to this topic, and reports payments made by Gilead, MSD, Janssen and 
      Therakos to suppliers for support for attending meetings and/or travel. IG 
      reports a "Rio Hortega" Grant (Plan Estatal de I + D + I 2013-2016. Plan Estatal 
      de Investigacion Cientifica y Tecnica y de Innovacion (2017-2020). Co-funded by 
      European Regional Development Fund/European Social Fund "A way to make 
      Europe"/"Investing in your future"). All other authors have nothing to declare.
EDAT- 2021/08/19 06:00
MHDA- 2021/08/19 06:01
PMCR- 2021/08/13
CRDT- 2021/08/18 06:32
PHST- 2021/08/18 06:32 [entrez]
PHST- 2021/08/19 06:00 [pubmed]
PHST- 2021/08/19 06:01 [medline]
PHST- 2021/08/13 00:00 [pmc-release]
AID - S2589-5370(21)00366-7 [pii]
AID - 101086 [pii]
AID - 10.1016/j.eclinm.2021.101086 [doi]
PST - ppublish
SO  - EClinicalMedicine. 2021 Sep;39:101086. doi: 10.1016/j.eclinm.2021.101086. Epub 
      2021 Aug 13.