Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome (THYTECH2)

The immune system is the body's defense system against pathogens and other harmful agents, but it is also responsible for transplant rejection or autoimmune diseases. Another scenario of disproportionate immune response is the Immune Hyperactivation, an exaggerated systemic inflammatory response such as that caused by respiratory infections like COVID-19, a major cause of acute respiratory distress syndrome (ARDS) in critically ill patients.

The standard treatment to prevent these immune responses is the use of immunosuppressive and immunomodulatory therapy, which produces a pleotropic inhibition on the immune system and have a high cost. However, a widespread feeling among the scientific community is that only re-educating immune system to promote immune tolerance will decline the harmful immune responses without prejudice to the functional integrity of the immune system.

In the context of severe COVID-19 and ARDS, it has been shown that an alteration in the frequency and functionality of Tregs. In addition, it has been described that the increased oxygen therapy requirements is not due to the viral effect, but to the triggered immune hyperinflammation that can lead to multi-organ failure and death. Therefore, although the adoptive transfer of Treg is a promising cell therapy for the treatment of this type of disease, the characteristics of the patients make it unfeasible to obtain enough Treg from the patient to produce a therapeutic dose and, if achieved, the quality of these cells does not allow a prolonged therapeutic effect to be obtained over time.

Tregs are a subset of CD4+ T cells with suppressive function that maintain the immune system balance. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical and clinical studies. To date, most of the clinical trials employing Treg cell therapy have been limited due to a small Treg numbers obtained (Treg cells represent less than 10% of CD4+ T cells) and the low quality of infused Treg (in terms of purity, survival, and suppressor capacity).

The investigators have developed an innovative Treg manufacturing protocol, that overcome the existing difficulties by employing a new source of cells, which is the thymic tissue routinely removed and discarded in paediatric cardiac surgeries. The protocol allows to produce massive amounts of thymus derived Treg cells (thyTreg), with improved survival, high suppressive capacity and suitable for therapeutic use.

The study will evaluate escalating doses of thyTreg administrated as a single IV dose. The study will include up to 2 cohorts of 4 to 8 subjects per each arm (control group and thyTreg group) followed for a total of 24 months. All subjects will receive standard of care treatment for COVID-19 or ARDS, including dexamethasone and other approved therapies from institutional guidelines.

• Length of intensive care unit stay [Срок оценки: 24 months]
• Oxygenation improvement as assessed using PaO2/FiO2 and/or SaO2/FiO2 [Срок оценки: 24 months]
• Change in clinical status as assessed using Sequential Organ Failure Assessment Score [Срок оценки: 24 months]
• Change in clinical status as assessed using Acute Physiology and Chronic Health disease Classification System (APACHE) III [Срок оценки: 24 months]
• Change in clinical status as assessed using Barthel score [Срок оценки: 24 months]
• Change in myocardial function as measured by mitral and tricuspid regurgitation using doppler echocardiography [Срок оценки: 24 months]
• Change in myocardial function as measured by mitral and tissue mitral doppler using doppler echocardiography [Срок оценки: 24 months]
• Change in myocardial function as measured by tricuspid and tissue tricuspid using doppler echocardiography [Срок оценки: 24 months]
• Change in SARS-CoV-2 positivity or etiology of ARDS assessed using diagnostics test [Срок оценки: 24 months]
• Change From Baseline in ferritin parameter [Срок оценки: 24 months]
• Change From Baseline in interleukin 6 (IL-6) [Срок оценки: 24 months]
• Change From Baseline in C-Reactive Protein (PCR) [Срок оценки: 24 months]