A potential drug in the armamentarium of post-cardiac transplantation immunosuppression: belatacept
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MINI REVIEW ARTICLE
A potential drug in the armamentarium of post-cardiac transplantation immunosuppression: belatacept Dhruva Sharma 1
&
Neha Sharma 2
Received: 17 April 2020 / Revised: 12 June 2020 / Accepted: 19 June 2020 # Indian Association of Cardiovascular-Thoracic Surgeons 2020
Abstract Undeterred by all the advancement in the field of cardiac transplantation, heart transplant rejection remained its mammoth quandary. Management of heart transplant recipients has drastically improved with current regimens of immunosuppressive drugs. The adverse effects of calcineurin inhibitors are lacking with the use of belatacept, which is a costimulation inhibitor that interferes with the interaction between CD28 on T cells and the B7 ligands on antigen-presenting cells. It was originally approved for use in renal transplant recipients but it has shown promising results in heart transplant recipients. Keywords Belatacept . Cardiac transplantation . Lung transplant . Immunosuppression
Introduction Heart transplantation is the last resort for patients with endstage heart failure (HF) who remain symptomatic in spite of maximal medical and device therapy. Undeterred by all the advancement in the field of cardiac transplantation, heart transplant rejection remained its mammoth quandary [1]. Management of heart transplant recipients has drastically improved with current regimens of immunosuppressive drugs including calcineurin inhibitors. Calcineurin inhibitors are associated with various adverse effects like cardiovascular, metabolic, neurologic, and renal complications that ultimately affect long-term survival in cardiothoracic transplant. Glomerular filtration rate is found to be reduced to even 30 ml by 5 years post-transplant, in about 20% patients [2]. These adverse effects are lacking with the use of belatacept which is a costimulation inhibitor that interferes with the interaction between CD28 on T cells and the B7 ligands on antigen-presenting cells [2, 3]. Bristol-Myers Squibb Company (BMS) got approval by the US Food and Drug Administration (FDA) in June 2011
* Dhruva Sharma [email protected] 1
Department of Cardiothoracic & Vascular Surgery, SMS Medical College & Attached Group of Hospitals, Jaipur, India
2
Department of Pharmacology, SMS Medical College, Jaipur, India
for belatacept to treat organ rejection in adult kidney transplant recipients [3]. It was originally approved for use in renal transplant recipients, but it has shown promising results in heart transplant recipients. No therapeutic drug monitoring is required and is only administered once a month [4].
Mechanism of action of belatacept Belatacept is intrinsically a fully human fusion protein of the CTLA4 extracellular domain, having fragments of the Tc domain of human IgG1. It results in the blockade of T cell activation, by binding to CD86/CD80 on the antigen-presenting cell [5, 6]. Abatacept was the first such molecule to inhibit signal-2 with high affinity for CD80/86. It is used in rheumatoid arthritis, psoriatic arthritis,
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