PHARMACOLOGICAL MODULATION OF THE ADAPTIVE IMMUNE SYSTEM IN ISCHAEMIC HEART DISEASE
type: CreativeWork
description: Inflammation plays a key role in the disease processes of both atherosclerosis and myocardial infarction (MI). Regulatory T (Treg) cells are a subset of the adaptive immune system involved in immune tolerance. Animal models show that increasing Treg cell numbers in atherosclerosis can limit disease progression. Several small clinical studies have used low dose interleukin-2 (ld-IL-2) to increase Treg cells in patients with various autoimmune but not cardiovascular diseases. Therefore, a phase 1/2a, randomised, placebo-controlled, double-blind, dose-escalation, two-part clinical trial was performed to test ld-IL-2 (aldesleukin) given once daily subcutaneously, for five consecutive days. In Part A, 25 patients with stable ischaemic heart disease were treated in 5 dose groups (0.3, 0.6, 1.2, 2.4 and 3 x106 IU/day); whilst in Part B, 16 patients with acute coronary syndrome were treated in two dose groups (1.5 and 2.5 x106 IU/day). Results showed that ld-IL-2 was safe and well tolerated across the dose range. The 1.5 x106 IU/day dose increased Treg cell levels by the pre-specified 75% and did not increase effector T cells numbers. There were additional novel findings in other immune cells and cytokine markers. B cell subsets in animal models worsen post-MI inflammation and remodelling. Antibody mediated depletion of B cells in mice limited myocardial injury and improved cardiac function. Rituximab is a monoclonal antibody targeted against human B cells and has been used in the treatment of certain autoimmune diseases and cancers. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, a phase 1/2a, open-label, dose-escalation, single-arm, clinical trial was set up to test rituximab in patients with ST-elevation MI. In total, 24 patients were treated in 4 escalating dose groups (200, 500, 700 and 1000 mg). Rituximab was administrated intravenously as a single dose within 48hours of symptoms onset. Rituximab was well tolerated a…
abstract: Inflammation plays a key role in the disease processes of both atherosclerosis and myocardial infarction (MI). Regulatory T (Treg) cells are a subset of the adaptive immune system involved in immune tolerance. Animal models show that increasing Treg cell numbers in atherosclerosis can limit disease progression. Several small clinical studies have used low dose interleukin-2 (ld-IL-2) to increase Treg cells in patients with various autoimmune but not cardiovascular diseases. Therefore, a phase 1/2a, randomised, placebo-controlled, double-blind, dose-escalation, two-part clinical trial was performed to test ld-IL-2 (aldesleukin) given once daily subcutaneously, for five consecutive days. In Part A, 25 patients with stable ischaemic heart disease were treated in 5 dose groups (0.3, 0.6, 1.2, 2.4 and 3 x106 IU/day); whilst in Part B, 16 patients with acute coronary syndrome were treated in two dose groups (1.5 and 2.5 x106 IU/day). Results showed that ld-IL-2 was safe and well tolerated across the dose range. The 1.5 x106 IU/day dose increased Treg cell levels by the pre-specified 75% and did not increase effector T cells numbers. There were additional novel findings in other immune cells and cytokine markers. B cell subsets in animal models worsen post-MI inflammation and remodelling. Antibody mediated depletion of B cells in mice limited myocardial injury and improved cardiac function. Rituximab is a monoclonal antibody targeted against human B cells and has been used in the treatment of certain autoimmune diseases and cancers. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, a phase 1/2a, open-label, dose-escalation, single-arm, clinical trial was set up to test rituximab in patients with ST-elevation MI. In total, 24 patients were treated in 4 escalating dose groups (200, 500, 700 and 1000 mg). Rituximab was administrated intravenously as a single dose within 48hours of symptoms onset. Rituximab was well tolerated a…
author: Zhao, Tian xiao
language: eng
keywords: Atherosclerosis, Myocardial infarction, Regulatory T cells, B cells
license: https://www.repository.cam.ac.uk/bitstreams/da17b4aa-54f5-43c3-9842-8b27353de7e9/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-02-07
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.55391