Monoclonal antibodies: A prospective and retrospective view.

2020 ◽  
Vol 27 ◽  
Author(s):  
Jwala Sivaccumar ◽  
Annamaria Sandomenico ◽  
Luigi Vitagliano ◽  
Menotti Ruvo
Keyword(s):  
Monoclonal Antibodies ◽  
Cardiovascular Diseases ◽  
Autoimmune Diseases ◽  
New Technologies ◽  
Clinical Applications ◽  
Structural Components ◽  
Retrospective View

Background: Monoclonal antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, angiogenesis-related diseases and more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering. Objectives: The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends. Results: We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables. Conclusions: The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.

scholarly journals Monitoring anti-B cell immunotherapies in autoimmune diseases: Go with the flow. A Position Paper of the Italian Society for Clinical Cell Analysis (ISCCA)

2019 ◽  
Vol 1 (2) ◽  
pp. 52-62
Author(s):  
Bruno Brando ◽  
Arianna Gatti ◽  
Alfredo Maria Lurati ◽  
Paola M.L. Faggioli
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cells ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Cell Activation ◽  
Biological Effects ◽  
Individual Response ◽  
Anti Cd20

During the past decades autoimmune diseases have been usually treated with immunosuppressive drugs mostly active on T-Cell mediated responses. Only in recent years, with our extended knowledge of the pathogenic mechanisms of autoreactive disorders and the tremendous development of new therapeutic monoclonal antibodies, anti-B-Cell therapies have emerged as a new option for treating autoimmune diseases. The rationale for this changeover from T-Cell to B-Cell targeted therapies resides in the recently accumulated evidence of the role of B-Cells in the pathogenesis of autoimmune diseases and in the generation of tissue damage. Targeting memory and effector BCells may then disrupt the production of pathogenic antibodies, counteract the role of B-Cells in sustaining antigen presentation to T-Cells and block the synthesis of B-Cell activation cytokines. The anti-CD20 monoclonal antibody Rituximab was first introduced more than 20 years ago for the treatment of CD20+ chronic B-lymphoproliferative disorders, and was then successfully experimented in the treatment of an ever-increasing spectrum of autoimmune diseases. Newer anti-CD20 monoclonal antibodies have been introduced more recently, which vary in their biological effects. The need for laboratory indicators that may help the rational usage and follow-up of anti-CD20 treatments has now emerged, due to the high variability of individual response, to the markedly different outcomes in the various diseases and to the controversial role of pathogenic autoantibodies as indicators of disease activity. Flow cytometric (FCM) analyses to identify and enumerate the B-cell functional subsets in the peripheral blood have been developed in recent years. They can be used to assess the degree and the persistence of memory B-Cell depletion, the quality and the timing of B-Cell reconstitution, along with the highly sensitive FCM counting technique needed for the detection of extremely low cell levels. The long-term aim of this innovative approach is to provide clinicians with a tool for a safer and more rational usage of anti-CD20 agents.

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.

scholarly journals Clinical Applications of Aspirin as a Multi-Potent Drug Beyond Cardiovascular Implications: A Proof of Concept for Anesthesiologists and a Narrative Review

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Aysa Rezabakhsh ◽  
Farnad Imani ◽  
Ata Mahmoodpoor ◽  
Maryam Soleimanpour ◽  
Kavous Shahsavarinia ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Clinical Applications ◽  
Narrative Review ◽  
Proof Of Concept ◽  
Potent Drug

: To the best of our knowledge, aspirin (ASA) is known as a commonly used medication worldwide. Although the cardiovascular aspects of ASA are well-established, recently, it has been identified that ASA can yield multiple extra-cardiovascular therapeutic potencies in facing neurodegenerative disorders, various cancers, inflammatory responses, and the COVID-19 pandemic. In this review, we aimed to highlight the proven role of ASA administration in the variety of non-cardiovascular diseases, particularly in the field of anesthesiology.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Gender, Technology and the New Woman

2017 ◽  
Author(s):  
Lena Wånggren
Keyword(s):  
Nineteenth Century ◽  
New Woman ◽  
New Technologies ◽  
Gender And Sexuality ◽  
Literary Texts ◽  
Late Nineteenth Century ◽  
Gender And Technology ◽  
The New Woman ◽  
Grant Allen

This book examines late nineteenth-century feminism in relation to technologies of the time, marking the crucial role of technology in social and literary struggles for equality. The New Woman, the fin de siècle cultural archetype of early feminism, became the focal figure for key nineteenth-century debates concerning issues such as gender and sexuality, evolution and degeneration, science, empire and modernity. While the New Woman is located in the debates concerning the ‘crisis in gender’ or ‘sexual anarchy’ of the time, the period also saw an upsurge of new technologies of communication, transport and medicine. This book explores the interlinking of gender and technology in writings by overlooked authors such as Grant Allen, Tom Gallon, H. G. Wells, Margaret Todd and Mathias McDonnell Bodkin. As the book demonstrates, literature of the time is inevitably caught up in a technological modernity: technologies such as the typewriter, the bicycle, and medical technologies, through literary texts come to work as freedom machines, as harbingers of female emancipation.

Parliament as the Foreign Policy Actor: the Resources of the Parliamentary Diplomacy

2018 ◽  
Vol 42 ◽  
pp. 316-321
Author(s):  
Boris I. Ananyev ◽  
Daniil A. Parenkov
Keyword(s):  
Foreign Policy ◽  
International Security ◽  
New Technologies ◽  
Conservative Approach ◽  
National Interests ◽  
Policy Actor ◽  
Security Challenges ◽  
Essential Idea ◽  
Per Se

The aim of the article is to show the role of parliament in the foreign policy within the framework of the conservative school of thought. The authors examine both Russian and Western traditions of conservatism and come to the conclusion that the essential idea of “the rule of the best” has turned to be one of the basic elements of the modern legislative body per se. What’s more, parliament, according to the conservative approach, tends to be the institution that represents the real spirit of the nation and national interests. Therefore the interaction of parliaments on the international arena appears to be the form of the organic communication between nations. Parliamentary diplomacy today is the tool that has the potential to address to the number of issues that are difficult to deal with within the framework of the traditional forms of IR: international security, challenges posed by new technologies, international sanctions and other.

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