scholarly journals The Relevance of Monoclonal Antibodies in the Treatment of COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 557
Author(s):  
Anabel Torrente-López ◽  
Jesús Hermosilla ◽  
Natalia Navas ◽  
Luis Cuadros-Rodríguez ◽  
José Cabeza ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
State Of The Art ◽  
Virus Protein ◽  
Immune Disorders ◽  
The Subject ◽  
New Treatments ◽  
Therapeutic Monoclonal Antibodies ◽  
Made In

Major efforts have been made in the search for effective treatments since the outbreak of the COVID-19 infection in December 2019. Extensive research has been conducted on drugs that are already available and new treatments are also under development. Within this context, therapeutic monoclonal antibodies (mAbs) have been the subject of widespread investigation focusing on two target-based groups, i.e., non-SARS-CoV-2 specific mAbs, that target immune system responses, and SARS-CoV-2 specific mAbs, designed to neutralize the virus protein structure. Here we review the latest literature about the use of mAbs in order to describe the state of the art of the clinical trials and the benefits of using these biotherapeutics in the treatment of COVID-19. The clinical trials considered in the present review include both observational and randomized studies. We begin by presenting the studies conducted using non-SARS-CoV-2 specific mAbs for treating different immune disorders that were already on the market. Within this group of mAbs, we focus particularly on anti-IL-6/IL-6R. This is followed by a discussion of the studies on SARS-CoV-2 specific mAbs. Our findings indicate that SARS-CoV-2 specific mAbs are significantly more effective than non-specific ones.

scholarly journals Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Francesca Bonello ◽  
Roberto Mina ◽  
Mario Boccadoro ◽  
Francesca Gay
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Plasma Cells ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Promising Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Antibody Drug

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.

scholarly journals Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Andrea Sierra-Sepúlveda ◽  
Alexia Esquinca-González ◽  
Sergio A. Benavides-Suárez ◽  
Diego E. Sordo-Lima ◽  
Adrián E. Caballero-Islas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
State Of The Art ◽  
Therapeutic Targets ◽  
Organ Damage ◽  
The State ◽  
Pathogenic Mechanism ◽  
Emerging Therapies

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

scholarly journals Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

2017 ◽  
Vol 24 (5) ◽  
Author(s):  
Paula M. Ladwig ◽  
David R. Barnidge ◽  
Maria A. V. Willrich
Keyword(s):  
Mass Spectrometry ◽  
Monoclonal Antibodies ◽  
Clinical Laboratory ◽  
Enzyme Linked Immunosorbent Assay ◽  
Measurement Tool ◽  
The Past ◽  
Therapeutic Drugs ◽  
Therapeutic Monoclonal Antibodies ◽  
Made In

ABSTRACT Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.

scholarly journals Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Puneet Rawat ◽  
Divya Sharma ◽  
Ambuj Srivastava ◽  
Vani Janakiraman ◽  
M. Michael Gromiha
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Effective Vaccine ◽  
Therapeutic Antibodies ◽  
Viral Neutralization ◽  
Investigational Drugs ◽  
Therapeutic Monoclonal Antibodies ◽  
Interaction Surface ◽  
Limited Choice

AbstractThe urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications.

scholarly journals CONSUMER CULTURE STUDIES, A GLANCE AT THE LITERATURE’S CONTRIBUTIONS TO THE CONCEPT

2020 ◽  
pp. 13-40
Author(s):  
Eduardo Norman-Acevedo ◽  
Juan Carlos Sosa-Varela ◽  
Adriana Bonomo ◽  
Violeta Corona-Cabrera
Keyword(s):  
Consumer Culture ◽  
Scientific Literature ◽  
State Of The Art ◽  
Selection Process ◽  
Culture Studies ◽  
Select Group ◽  
Important Input ◽  
The Subject ◽  
Made In ◽  
Do So

Publishing a book on consumer culture studies originates from the need to review research conducted on this subject. Among the expectations of Politécnico Grancolombiano Institución Universitaria, and as a result of reviews on the subject, this opportunity was identified within scientific literature. This book intends to be useful for readers by identifying international research trends in this field. It also aims to support the decision-making of marketing managers, with respect to consumers, and to have important input that fosters future research.To do so, the institution introduces the structure of this editorial project, which first identified relevant authors and made an initial call to authors based on an approach to the state of the art by implementing a systematic literature review (SLR) (Kitchenham, 2004). The call made in August 2017 proposed that a select group of authors participate in the project with a chapter of its structure, given that they have indicated their interest in the subject. This proposal received great reception among those invited, including eight articles submitted, from which, after a rigorous selection process, contributions of five chapters were included at the date of publication with participation from international researchers who believed in our project.

Clinical Evaluation of New Drugs

PEDIATRICS ◽  
1959 ◽  
Vol 24 (5) ◽  
pp. 733-733
Keyword(s):  
Clinical Trials ◽  
Clinical Evaluation ◽  
New Drugs ◽  
Wide Range ◽  
The Subject ◽  
Made In

This book is a collection of essays by authors of established repute. The essays outline the general principles and important points to be kept in mind in the evaluation of drugs. The contents cover a wide range of topics from statistics to ethics. The objective of the series of essays is to improve the calibre of clinical trials in order to define the potentials of new drugs more accurately and rapidly, and also to present standards which should enable the practitioner and student to be more critical in judging the reports of clinical trials and the claims which are made in the promotion of new drugs. The book will probably be most useful in furnishing an introduction to the subject.

scholarly journals Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 618-629
Author(s):  
Bonnie J.B. Lewis ◽  
Donald R. Branch
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Mouse Models ◽  
Preclinical Testing ◽  
Systemic Complications ◽  
Chronic Autoimmune Disease

<b><i>Background:</i></b> Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (FcγRs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models to target FcγR function, with the focus being on drugs that have been made from the Fc of immunoglobulin G (IgG). <b><i>Summary:</i></b> Evidence suggests that FcγRs play a major role in immune complex-induced inflammation in autoimmune diseases, such as RA. However, there is limited knowledge on the importance of FcγRs in the human disease even though there has been extensive work in mouse models of RA. Numerous mouse models of RA are available, with each model depicting certain aspects of the disease. Induced models of RA have nonspecific immune activation with cartilage-directed autoimmunity, whereas spontaneous models of RA develop without immunization, which results in a more chronic form of arthritis. These models have been used to test FcγR-targeting monoclonal antibodies, intravenous immunoglobulin (IVIg), subcutaneously administered IVIg, and recombinant Fcs for their ability to interact with and modify FcγR function. Recombinant Fcs avidly bind FcγRs and exhibit enhanced therapeutic efficacy in mouse models of RA. <b><i>Key Message:</i></b> The therapeutic utility of targeting FcγRs with recombinant Fcs is great and should be explored in human clinical trials for autoimmune diseases, such as RA.

Engineering therapeutic antibodies for patient safety: tackling the immunogenicity problem

2020 ◽  
Vol 33 ◽  
Author(s):  
Michael Ulitzka ◽  
Stefania Carrara ◽  
Julius Grzeschik ◽  
Henri Kornmann ◽  
Björn Hock ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Immune System ◽  
Immune Responses ◽  
Foreign Protein ◽  
Therapeutic Antibodies ◽  
T Cell Epitopes ◽  
Post Translational Modifications ◽  
Human Antibodies ◽  
Therapeutic Monoclonal Antibodies ◽  
In Silico Methods

Abstract Established monoclonal antibodies (mAbs) allow treatment of cancers, autoimmune diseases and other severe illnesses. Side effects either arise due to interaction with the target protein and its biology or result from of the patient’s immune system reacting to the foreign protein. This immunogenic reaction against therapeutic antibodies is dependent on various factors. The presence of non-human sequences can trigger immune responses as well as chemical and post-translational modifications of the antibody. However, even fully human antibodies can induce immune response through T cell epitopes or aggregates. In this review, we briefly describe, how therapeutic antibodies can interact with the patient’s immune system and summarize recent advancements in protein engineering and in silico methods to reduce immunogenicity of therapeutic monoclonal antibodies.

scholarly journals High Efficacy of Therapeutic Equine Hyperimmune Antibodies Against SARS-CoV-2 Variants of Concern

2021 ◽  
Vol 8 ◽  
Author(s):  
Andres Moreira-Soto ◽  
Mauricio Arguedas ◽  
Hebleen Brenes ◽  
Willem Buján ◽  
Eugenia Corrales-Aguilar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Costa Rica ◽  
Polyclonal Antibodies ◽  
Low Cost ◽  
High Efficacy ◽  
Low Concentrations ◽  
Alpha Beta ◽  
Therapeutic Monoclonal Antibodies ◽  
Treatment Alternatives

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsilon, gamma and delta, using plaque reduction neutralization assays. We show that equine pAbs efficiently neutralize the variants of concern, with inhibitory concentrations in the range of 0.146–1.078 μg/mL, which correspond to extremely low concentrations when compared to pAbs doses used in clinical trials. Equine pAbs are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

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