The Effect of Low-dose Interleukin-2 on the Immune Landscape of Human Atherosclerotic Plaques at Single Cell Resolution.
- Conditions
- TIACarotid AtherosclerosisCarotid Artery Plaque
- Interventions
- Procedure: Standard care - Carotid Endarterectomy
- Registration Number
- NCT05975554
- Brief Summary
The goal of this clinical trail is to compare the differences in carotid plaque Treg cells' gene signature for activation, proliferation, and suppressive function using scRNA-seq in patients treated with IL-2 compared to control.
- Detailed Description
Up till now our Lab has looked at Tregs and immune cells in the blood. The question remains whether low dose IL-2 can have the desired effect on Tregs in atherosclerotic plaques where they could alter the pathophysiology and potentially clinical outcomes for patients.
Up until recently, the cellular composition and cell-specific expression patterns of human atherosclerotic plaques remained elusive. However, recent breakthroughs studies using scRNA-seq, CITE-seq, and single-cell ATAC-seq on human carotid plaques have offered important insight into plaque composition, cell heterogeneity, and cell-cell interactions giving new perspectives on mechanisms of disease. The next logical stage is to use this new insight and powerful biological tool to assist in drug development for patients.
Therefore, the aims of the study are:
1. To assess if low dose IL-2, given systemically to patients at our proposed dose, can alter Tregs in atherosclerotic plaques (the disease tissue) to exhibit a proliferating, activated, and immunosuppressive phenotype
2. To assess if modulating plaque Tregs can cause a shift in the plaque immune landscape to a less inflammatory phenotype
3. To study the relationship between plaque and circulating immune cells after systemic immune modulation
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Presence of carotid stenosis on either ultrasound or CT scan.
- Planned to undergo carotid endarterectomy.
- Autoimmune disease
- Any regular immunosuppressive treatment [Inhaled or topical steroids are permissible]
- Modified Rankin Scale score of ≥4 at screening
- Known active hepatic disease or alanine aminotransferase (ALT) > 2xULN
- Severe chronic kidney disease (defined as eGFR < 30 ml/min/1.73m2)
- Allergy or intolerance to aldesleukin
- Signs or symptoms of active infection
- History of human immunodeficiency virus (HIV), hepatitis B or C
- Current malignancy requiring active treatment
- Vaccine within 4 weeks prior to screening or plans for vaccination during study period
- Women of child-bearing potential and pregnancy
- Women who are breast-feeding
- Clinically relevant medical or surgical conditions that, in the opinion of the
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low dose interleukin-2 Interleukin-2 [IL-2] Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Control Standard care - Carotid Endarterectomy Standard of care treatment Low dose interleukin-2 Standard care - Carotid Endarterectomy Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC.
- Primary Outcome Measures
Name Time Method Difference in gene expression in Tregs Time of surgery Comparing differential gene expression using scRNA-seq technologies, from isolated Tregs from carotid plaques from the two patient groups (IL-2 treatment and control). Differential gene expression will be assessed using standard techniques (Z-Score)
- Secondary Outcome Measures
Name Time Method Difference in gene expression in Teff cells. Time of surgery Comparing differential gene expression using scRNA-seq technologies, from isolated Teffs from carotid plaques from the two patient groups (IL-2 treatment and control). Differential gene expression will be assessed using standard techniques (Z-Score)
Difference in gene expression patterns in Treg & Teff cells. Baseline and at time of surgery Comparison between Treg and Teff cells collected at baseline and day of surgery will be compared between IL-2 and control groups. Differential gene expression will be assessed using standard techniques (Z-Score)
Immune cell gene signature, in plaque and blood. Time of surgery Difference in immune cell gene signature will be compared using scRNA-seq in both plaque and blood samples, and further compared between IL-2 and control groups. Comparative analysis will be completed using gene set enrichment analysis (Enrichment Score).
Trial Locations
- Locations (1)
Addenbrookes Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom