Allogeneic umbilical cord-derived mesenchymal stromal cells as treatment for systemic lupus erythematosus: a single-centre, open-label, dose-escalation, phase 1 study

被引：0

作者：

Farge, Dominique ^{[1
,2
,3
]}

Biard, Lucie ^{[4
]}

Weil, Ben ^{[5
]}

Girault, Virginie ^{[6
,7
]}

Lansiaux, Pauline ^{[1
,2
]}

Munia, Ingrid ^{[1
,2
]}

Loisel, Severine ^{[6
,7
]}

Charles, Catney ^{[1
,2
]}

Saout, Judikael ^{[6
,7
]}

Resche-Rigon, Matthieu ^{[4
]}

Korganow, Anne Sophie ^{[8
]}

Beuvon, Clement ^{[9
]}

Pugnet, Gregory ^{[10
]}

Cacciatore, Carlotta ^{[1
,2
]}

Abisror, Noemie ^{[11
]}

Taupin, Jean Luc ^{[12
]}

Cras, Audrey ^{[13
,14
,15
]}

Lowdell, Mark W. ^{[16
]}

Tarte, Karin ^{[6
,7
]}

机构：

[1] Hop St Louis, AP HP, Maladies Autoimmunes & Therapie Cellulaire, Unite Med Interne UF CRMR 04,Ctr Reference des Ma, F-75010 Paris, France

[2] Univ Paris Cite, IRSL, Rech Clin Hematol Immunol & Transplantat, URP3518, Paris, France

[3] McGill Univ, Dept Med, Montreal, PQ, Canada

[4] Univ Paris Cite, Hop St Louis, AP HP, INSERM,Serv Biostat & Informat Med DMU PRISME,Tea, Paris, France

[5] Royal Free London NHS Fdn Trust, London, England

[6] CHU Rennes, Etab Francais Sang Bretagne, SITI, Rennes, France

[7] Univ Rennes, INSERM, UMR 1236, Etab Francais Sang Bretagne, F-35043 Rennes, France

[8] Univ Strasbourg, Hop Univ Strasbourg, Ctr Natl Reference Malad Autoimmunes RESO, Dept Immunol Clin,INSERM,U1109, Strasbourg, France

[9] CHU Poitiers, Serv Med Interne, 2 Rue Miletrie, Poitiers, France

[10] CHU Rangueil, Pole Hosp Univ Maladies Digest, Serv Med Interne & Immunol Clin, Toulouse, France

[11] Sorbonne Univ, Hop St Antoine, AP HP, Serv Med Interne, Paris, France

[12] Univ Paris Cite, Hop St Louis, AP HP, INSERM U976,HIPI,IRSL,Lab Immunol & Histocompatib, Paris, France

[13] St Louis Hosp, AP HP, Cell Therapy Unit, Paris, France

[14] Univ Paris Cite, INSERM, UMR1140, Paris, France

[15] INSERM, CIC Biotherapies CBT501, Paris, France

[16] Univ London, London, England

来源：

LANCET RHEUMATOLOGY | 2025年 / 7卷 / 04期

关键词：

STEM-CELLS;

D O I：

10.1016/S2665-9913(24)00298-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE. Methods This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the SaintLouis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 x 106, 2 x 106, or 4 x 106 umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 x 106 cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade >= 3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29. Findings From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 x 106 dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 x 106 cells per kg (range 2 x 106 to 4 x 106). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12<middle dot>4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse. Interpretation Our results suggest that a single infusion of 2 x 106 cells per kg or 4 x 106 cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to confirm clinical efficacy and the role of B-cell modifications in clinical benefit. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

引用

页码：e261 / e273

页数：13