Abstract: RESEARCH LETTER
TO THE EDITOR:
Randomized, double-blinded, placebo-controlled trial of allogeneic
cord blood T-regulatory cells for treatment of COVID-19 ARDS
1
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY; 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns
Hopkins University, Baltimore, MD; 3 Department of Medicine, Baylor College of Medicine, Houston, TX; 4 Department of Lymphoma/Myeloma, The University of Texas MD
Anderson Cancer Center, Houston, TX; 5 Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, The University of North Carolina at Chapel Hill,
Chapel Hill, NC; 6 Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest School of Medicine, Winston-Salem, NC; 7 Division of Pulmonary,
Allergy, and Critical Care Medicine, Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, and Center for Acute Respiratory Failure, New
York-Presbyterian Hospital, New York, NY; 8 Department of Biostatistics, MD Anderson Cancer Center, Houston, TX; 9 Cellenkos Inc., Houston, TX; 10 Division of Hematology/
Oncology, Department of Medicine, New York-Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY; 11 Mass General Hospital, Biostatistics,
Boston, MA; and 12 Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto and University of Toronto, Toronto, Canada
Regulatory T cells (Tregs) characterized by cell surface expression of CD4+, CD25+, CD127low, and
high expression of intracellular FOXP3+ compromise 1% to 2% of total lymphocytes.1 Tregs can
suppress exuberant immune responses as observed in coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS),2 and clear residual inflammatory cells in the lung.3,4
Lyu et al demonstrated that multiple injections of allogeneic Treg cells derived from umbilical cord blood
(UCB) can decrease CD8+ pathogenic T cells in vivo leading to resolution of pulmonary inflammation.5
Gladstone et al reported that multiple infusions of allogeneic UCB Tregs at a fixed dose of 100 million
cells6 was associated with clinical improvement which correlated with decrease in inflammatory burden
in 2 patients with COVID-19 ARDS who had multiorgan failure requiring vasopressors and
hemodialysis.7
Based on these data, we performed a phase 1, randomized, multicenter, double-blinded, placebocontrolled clinical trial (www.clinicaltrials.gov #NCT04468971) in patients with COVID-19 ARDS to
examine the safety and early efficacy of CK0802, an off-the-shelf, cryopreserved, allogeneic UCB Treg
cell product that does not require human leukocyte antigen matching. Eligibility criteria included
diagnosis of SARS-CoV-2 infection, moderate-to-severe ARDS,8 intubated <120 hours, age ≥18
years, and ability to obtain informed consent. Patients were randomized in a 1:1:1 ratio to placebo, 100
million Tregs (CK0802-100), or 300 million Tregs (CK0802-300) per infusion on day 0 (ie, day of first
infusion), day 3(±1), and day 7(±1), constrained to 15 patients in each arm (total n = 45). The trial was
approved by the institutional review board and conducted in accordance with the Declaration of
Helsinki.
The CK0802 product was generated from 8 manufacturing campaigns (average 4429 × 106 Treg cells
per run [range, 1137-11 349 ×106]), which were subsequently cryopreserved. All products met the
release..
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