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Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity

SIMPLE SUMMARY: The application of immunotherapies to treat cancer patients has significantly improved over the last two decades and extended many patients’ life spans. Monoclonal antibodies are synthetic proteins employed as immunotherapies to treat and manage cancers that require a complete unders...

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Autores principales: Kumar, Mohit, Thangavel, Chellappagounder, Becker, Richard C., Sadayappan, Sakthivel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795565/
https://www.ncbi.nlm.nih.gov/pubmed/33396766
http://dx.doi.org/10.3390/cancers13010086
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author Kumar, Mohit
Thangavel, Chellappagounder
Becker, Richard C.
Sadayappan, Sakthivel
author_facet Kumar, Mohit
Thangavel, Chellappagounder
Becker, Richard C.
Sadayappan, Sakthivel
author_sort Kumar, Mohit
collection PubMed
description SIMPLE SUMMARY: The application of immunotherapies to treat cancer patients has significantly improved over the last two decades and extended many patients’ life spans. Monoclonal antibodies are synthetic proteins employed as immunotherapies to treat and manage cancers that require a complete understanding of cancer biology and the host’s immune system. However, activated immune responses, by monoclonal antibodies, can target nonspecific cancer cells, causing frequent immune-related adverse events that can lead to permanent disorders among cancer patients. The immune-related adverse events pose a risk of cardiac toxicity that includes hypertension, heart failure, arrhythmias, and left ventricular dysfunction during and after monoclonal antibody immunotherapy. Moreover, with the mortality rate of 47% attributed to heart disease and cancer, it is imperative to employ reliable, sensitive, and clinically relevant models for efficacy and safety assessment of immune drugs for cancer and the prevention of cardiotoxicities. ABSTRACT: Immunotherapy is one of the most effective therapeutic options for cancer patients. Five specific classes of immunotherapies, which includes cell-based chimeric antigenic receptor T-cells, checkpoint inhibitors, cancer vaccines, antibody-based targeted therapies, and oncolytic viruses. Immunotherapies can improve survival rates among cancer patients. At the same time, however, they can cause inflammation and promote adverse cardiac immune modulation and cardiac failure among some cancer patients as late as five to ten years following immunotherapy. In this review, we discuss cardiotoxicity associated with immunotherapy. We also propose using human-induced pluripotent stem cell-derived cardiomyocytes/ cardiac-stromal progenitor cells and cardiac organoid cultures as innovative experimental model systems to (1) mimic clinical treatment, resulting in reproducible data, and (2) promote the identification of immunotherapy-induced biomarkers of both early and late cardiotoxicity. Finally, we introduce the integration of omics-derived high-volume data and cardiac biology as a pathway toward the discovery of new and efficient non-toxic immunotherapy.
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spelling pubmed-77955652021-01-10 Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity Kumar, Mohit Thangavel, Chellappagounder Becker, Richard C. Sadayappan, Sakthivel Cancers (Basel) Review SIMPLE SUMMARY: The application of immunotherapies to treat cancer patients has significantly improved over the last two decades and extended many patients’ life spans. Monoclonal antibodies are synthetic proteins employed as immunotherapies to treat and manage cancers that require a complete understanding of cancer biology and the host’s immune system. However, activated immune responses, by monoclonal antibodies, can target nonspecific cancer cells, causing frequent immune-related adverse events that can lead to permanent disorders among cancer patients. The immune-related adverse events pose a risk of cardiac toxicity that includes hypertension, heart failure, arrhythmias, and left ventricular dysfunction during and after monoclonal antibody immunotherapy. Moreover, with the mortality rate of 47% attributed to heart disease and cancer, it is imperative to employ reliable, sensitive, and clinically relevant models for efficacy and safety assessment of immune drugs for cancer and the prevention of cardiotoxicities. ABSTRACT: Immunotherapy is one of the most effective therapeutic options for cancer patients. Five specific classes of immunotherapies, which includes cell-based chimeric antigenic receptor T-cells, checkpoint inhibitors, cancer vaccines, antibody-based targeted therapies, and oncolytic viruses. Immunotherapies can improve survival rates among cancer patients. At the same time, however, they can cause inflammation and promote adverse cardiac immune modulation and cardiac failure among some cancer patients as late as five to ten years following immunotherapy. In this review, we discuss cardiotoxicity associated with immunotherapy. We also propose using human-induced pluripotent stem cell-derived cardiomyocytes/ cardiac-stromal progenitor cells and cardiac organoid cultures as innovative experimental model systems to (1) mimic clinical treatment, resulting in reproducible data, and (2) promote the identification of immunotherapy-induced biomarkers of both early and late cardiotoxicity. Finally, we introduce the integration of omics-derived high-volume data and cardiac biology as a pathway toward the discovery of new and efficient non-toxic immunotherapy. MDPI 2020-12-30 /pmc/articles/PMC7795565/ /pubmed/33396766 http://dx.doi.org/10.3390/cancers13010086 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kumar, Mohit
Thangavel, Chellappagounder
Becker, Richard C.
Sadayappan, Sakthivel
Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title_full Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title_fullStr Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title_full_unstemmed Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title_short Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity
title_sort monoclonal antibody-based immunotherapy and its role in the development of cardiac toxicity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795565/
https://www.ncbi.nlm.nih.gov/pubmed/33396766
http://dx.doi.org/10.3390/cancers13010086
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