LILACS
Research type
Research Study
Full title
Low dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS)
IRAS ID
168647
Contact name
Dr Joseph Cheriyan
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eudract number
2014-004979-23
Clinicaltrials.gov Identifier
RCAG/521, Task 3, BHF CRE; mallatt 221214, BRC
Duration of Study in the UK
1 years, 3 months, 1 days
Research summary
Research Summary
Coronary artery disease (CAD) represents a major cause of morbidity and mortality worldwide and there is considerable need for new therapies to limit CAD burden. This application builds on solid pre-clinical research and novel therapeutic concepts developed by the applicants to target the immune response in patients with CAD. We have shown that the development and progression of atherosclerosis are promoted by an imbalance between pro-atherogenic Th1 effector (Teff) and anti-atherogenic T regulatory (Treg) cells. Here, we propose to re-establish a healthy immune balance in CAD patients through promotion of Treg cells using low-dose interleukin (IL)-2.
We hypothesize that low doses of IL-2 in patients with stable ischaemic heart disease as well as in those with ACS can increase Treg number and function, and ultimately promote plaque stabilisation and myocardial healing (this will be further addressed in future studies). In this context, it may improve patient recovery and limit the occurrence/recurrence of major clinical events.Summary of Results
A heart attack triggers the body’s immune cells to rush to the damaged heart and surrounding blood vessels. However, instead of having a healing effect, this can cause further harm, increasing the risk of future heart attack, stroke, and heart failure. Right now, there are no treatments available to counter this damaging immune response.
LILACS was a phase 2a clinical trial and has shown that low doses of the drug called aldesleukin could improve recovery after a heart attack by stopping this harmful feedback loop. If proven effective in larger clinical trials, the researchers hope it could be used to treat patients in the future.
High doses of aldesleukin stimulate the immune system to attack cancer cells. LILACS investigated whether using doses a thousand times lower than those used in cancer treatment could selectively target and boost anti-inflammatory cells in patients’ immune system.
In the trial, 16 patients admitted to hospital with a heart attack were given one of two doses of aldesleukin or a placebo. The drug was injected under the skin in their abdomen once a day for five days, and they were then followed up again a week after they had received the final dose of the drug.
The patients who received aldesleukin had a significantly greater increase in the number of regulatory T cells, a type of white blood cell that calms inflammation, a week after their last dose of aldesleukin compared to those who received a placebo.
Further analysis revealed that not only were the numbers of regulatory T cells increasing, but the cells themselves were also becoming more anti-inflammatory.
Low doses of aldesleukin also decreased the levels of other types of immune cells that can have damaging effects on inflammation and recovery after a heart attack. This might be another way that the drug could promote healing.
Encouraged by these results the researchers instigated a larger clinical trial to investigate whether low doses of aldesleukin after a heart attack can reduce inflammation in patient’s blood vessels. This trial is now closed to recruitment and is awaiting final analysis.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
17/NW/0012
Date of REC Opinion
14 Feb 2017
REC opinion
Further Information Favourable Opinion