CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Patient over 18 to 65 years of age
2. Patient Informed and non-opposed to the research by his medical doctor during hospitalization
3. Patient with clinical, radiological, gasometric and immunological criteria defined as:

   1. Acute respiratory failure secondary to acute lung injury of noncardiogenic cause
   2. Pulmonary abnormalities compatible with bilateral alveoloinsterstitial infiltrates by chest imaging (radiograph or scan)
   3. PaO2/FiO2≤ 300 Presence of at least one of the following markers of inflammation: IL6 \> 40 pg/ml or ferritin \>300 ng/ml or CRP \>3 mg/dl or increasing over the last 24 hours

Exclusion Criteria:

1. Pregnancy or breast feeding
2. Body mass index \>35
3. Patients not expected to survive 48 hours after enrolment based on clinical assessment
4. Patients with an extracorporeal respiratory support
5. Neutropenia (absolute neutrophil count \<1000/uL)
6. Thrombocytopenia (absolute neutrophil count \<50000/uL)
7. Positive serology for HBV, HCV, or HIV at Screening
8. Life expectancy of less than 6 months due to other pathologies
9. History of significant underlying pulmonary disease requiring oxygen therapy prior to inclusion.
10. Patients with a history of autoimmune diseases
11. Patients with a history of hematopoietic neoplasia or oncology disease
12. Patients with a history of hematopoietic or solid organ transplant
13. Patients with a congenital or induced immunodeficiency
14. Patients received thymoglobulin, basiliximab or any anti-T-cell therapies within 6 moths prior to the screening visit
15. Patients received other cell therapy in the last 12 months
16. Patients received intravenous immunoglobulin (IVIg) within 5 moths prior to the screening visit
17. Patients who have participated or is participating in a clinical research study evaluating COVID-19 or ARDS within 30 days prior to the screening visit

主要终点：1. Incidence of infusion-related adverse events (safety) by type, frequency, severity, and causality · 24 months
次要终点：Length of intensive care unit stay；Oxygenation improvement as assessed using PaO2/FiO2 and/or SaO2/FiO2；Change in clinical status as assessed using Sequential Organ Failure Assessment Score；Change in clinical status as assessed using Acute Physiology and Chronic Health disease Classification System (APACHE) III；Change in clinical status as assessed using Barthel score；Change in myocardial function as measured by mitral and tricuspid regurgitation using doppler echocardiography；Change in myocardial function as measured by mitral and tissue mitral doppler using doppler echocardiography；Change in myocardial function as measured by tricuspid and tissue tricuspid using doppler echocardiography

• Phase A: 5.000.000 thyTreg /kg · EXPERIMENTAL · Allogeneic thyTreg 5.000.000
• Phase A: standard of care · NO_INTERVENTION · Standard of care
• Phase B: 10.000.000 thyTreg /kg · EXPERIMENTAL · Allogeneic thyTreg 10.000.000
• Phase B: standard of care · NO_INTERVENTION · Standard of care

The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with preliminary results indicating the feasibility and safety of the therapy. In addition, thyTreg cells have shown low immunogenicity in the pre-clinical setting, indicating that allogeneic use of these thyTreg cells (allo-thyTreg) would have a low risk of adverse effects. These thyTreg cells could inhibit an excessive inflammation in SARS-CoV-2 infection, or ameliorate the immunological affection underlying Acute respiratory distress syndrome, improving life-threatening manifestations, restoring immune balance, and protecting affected tissues. This clinical trial is an open-label Sequential Parallel Group Phase I/II study to evaluate the safety and efficacy of allogeneic thymus derived Tregs (thyTreg) (thyTreg) in controlling the immune dysregulation associated with SARS-CoV-2 infection and/or Acute Respiratory Distress Syndrome.