Immune Modulation in Heart Failure: the Promise of Novel Biologics

Abstract

Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising. The potential of cell therapy for immune modulation is increasingly recognized in clinical trials. Strategies targeting anti-cardiac antibodies such as immunoadsorption and intravenous immunoglobulin have been used in clinical practice with positive outcomes but large pragmatic clinical trials are lacking. The use of an aptamer to block anti-cardiac antibodies is undergoing phase 1 clinical evaluation. Promising targets include inflammasomes, toll-like receptors, chemokines, natural killer cells, and macrophages. Large-scale immune modulatory clinical trials have been negative. Nevertheless, the experience gained from them along with increasing understanding of molecular mechanisms of immune pathophysiology in heart failure is leading to rapid recognition of new therapeutic targets and approaches.

The role of B cells in heart failure and implications for future immunomodulatory treatment strategies

“…93 Novel strategies targeting other immune components are currently undergoing evaluation in clinical trials. 94 Here, considering the evidence described earlier, we discuss and evaluate the possibility of new treatment strategies that directly target B cells in HF.…”

A Three-Part, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Mode of Action of BC 007, Neutraliser of Pathogenic Autoantibodies Against G-Protein Coupled Receptors in Healthy, Young and Elderly Subjects

“…BC 007 has shown its f GPCR-AAbneutralising effect in vitro [12], in spontaneously hypertensive rats in vivo [16] and recently with outcome benefit in f β1-AR-AAb positive Doberman pinschers with dilated cardiomyopathy [24]. Currently, it is under development for the causal treatment of diseases which are associated with the occurrence of f GPCR-AAbs (for review see [25]), such as HF here the β 1 -AR-AAb [4,26].…”

“…Up-to-date identified factors which trigger HF are manifold, as summarised in a comprehensive review by Hershberger et al [3]. The impact of autoimmunity on HF pathogenesis is also subject of current discussion [4]. In particular, with the positive outcome after the removal of agonistic acting autoantibodies which stimulate the β 1 -adrenoceptors (β 1 -AR), using immunoadsorption, a…”

Activation of T Lymphocytes as a Novel Mechanism in Beta1-Adrenergic Receptor Autoantibody-Induced Cardiac Remodeling—Additional Information About TLR9 Involvement

“…Both studies together complete a general understanding of the effects of TLR9 on the initiation and subsequent mainte-nance of heart failure that creates a vicious circle by making TLR9 essential in autoantibody formation [4], which in turn, stimulate receptors in heart cells and T lymphocytes [1].…”

“…Via the latter, the autoantibodies caused IL-6 release which is, according to their results, a further contributing factor to the pathogenesis of heart failure. Their observation bridges heart failure to an immunological perspective, a perspective which was recently comprehensively reviewed by Alvarez and Briasoulis [4] including current and novel treatment strategies.…”