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Trends in Biotechnology Jan 2019The monoclonal antibody (mAb) market has changed rapidly in the past 5 years: it has doubled in size, becoming dominated by fully human molecules, launched bispecific... (Review)
Review
The monoclonal antibody (mAb) market has changed rapidly in the past 5 years: it has doubled in size, becoming dominated by fully human molecules, launched bispecific molecules, and faced competition from biosimilars. We summarize the market in terms of therapeutic applications, type and structure of mAbs, dominant companies, manufacturing locations, and emerging markets.
Topics: Antibodies, Monoclonal; Global Health; Humans; Immunologic Factors; Immunotherapy
PubMed: 29945725
DOI: 10.1016/j.tibtech.2018.05.014 -
Molecular Pathology : MP Jun 2000Monoclonal antibodies are essential tools for many molecular immunology investigations. In particular, when used in combination with techniques such as epitope mapping... (Review)
Review
Monoclonal antibodies are essential tools for many molecular immunology investigations. In particular, when used in combination with techniques such as epitope mapping and molecular modelling, monoclonal antibodies enable the antigenic profiling and visualisation of macromolecular surfaces. In addition, monoclonal antibodies have become key components in a vast array of clinical laboratory diagnostic tests. Their wide application in detecting and identifying serum analytes, cell markers, and pathogenic agents has largely arisen through the exquisite specificity of these unique reagents. Furthermore, the continuous culture of hybridoma cells that produce these antibodies offers the potential of an unlimited supply of reagent. In essence, when compared with the rather limited supply of polyclonal antibody reagents, the feature of a continuous supply enables the standardisation of both the reagent and the assay technique. Clearly, polyclonal and monoclonal antibodies have their advantages and disadvantages in terms of generation, cost, and overall applications. Ultimately, monoclonal antibodies are only produced when necessary because their production is time consuming and frustrating, although greatly rewarding (at least most of the time!). This is especially apparent when a monoclonal antibody can be applied successfully in a routine pathology laboratory or can aid in the clinical diagnosis and treatment of patients. In this article, the generation and application of monoclonal antibodies are demystified to enable greater understanding and hopefully formulate novel ideas for clinicians and scientists alike.
Topics: Antibodies, Monoclonal; Humans; Hybridomas; Neoplasms
PubMed: 10897328
DOI: 10.1136/mp.53.3.111 -
The Lancet. Oncology Jun 2016Antibody-drug conjugates are monoclonal antibodies conjugated to cytotoxic agents. They use antibodies that are specific to tumour cell-surface proteins and, thus, have... (Review)
Review
Antibody-drug conjugates are monoclonal antibodies conjugated to cytotoxic agents. They use antibodies that are specific to tumour cell-surface proteins and, thus, have tumour specificity and potency not achievable with traditional drugs. Design of effective antibody-drug conjugates for cancer therapy requires selection of an appropriate target, a monoclonal antibody against the target, potent cytotoxic effector molecules, and conjugation of the monoclonal antibody to cytotoxic agents. Substantial advances in all these aspects in the past decade have resulted in regulatory approval of ado-trastuzumab emtansine and brentuximab vedotin for clinical use. Several promising antibody-drug conjugates are now in late-phase clinical testing. Ongoing efforts are focused on identifying better targets, more effective cytotoxic payloads, and further improvements in antibody-drug linker technology. Improved understanding of the mechanistic basis of antibody-drug conjugate activity will enable design of rational combination therapies with other agents, including immunotherapy.
Topics: Antibodies, Monoclonal; Humans; Immunoconjugates; Neoplasms
PubMed: 27299281
DOI: 10.1016/S1470-2045(16)30030-4 -
Neurotherapeutics : the Journal of the... Apr 2022Autoimmune diseases of the peripheral nervous system have so far been treated mainly with exogenous high-dose intravenous immunoglobulins (IVIg), that act through... (Review)
Review
Autoimmune diseases of the peripheral nervous system have so far been treated mainly with exogenous high-dose intravenous immunoglobulins (IVIg), that act through several mechanisms, including neutralization of pathogenic autoantibodies, modulation of lymphocyte activity, interference with antigen presentation, and interaction with Fc receptors, cytokines, and the complement system. Other therapeutic strategies have recently been developed, in part to address the increasing shortage of IVIg, prime among which is the use of B cell depleting monoclonal antibodies, or small molecule inhibitors targeting the B-cell specific kinases. Rituximab, a chimeric monoclonal antibody against CD20 + B lymphocytes, is currently the most used, especially in anti-MAG antibody neuropathy and autoimmune neuropathies with antibodies to nodal/paranodal antigens that are unresponsive to IVIg. After several reports of its efficacy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), rituximab is currently under investigation in three Phase 2 trials in CIDP. In addition, the possible role of complement activation in the pathogenesis of chronic autoimmune neuropathies has brought into consideration drugs that can block the complement cascade, such as eculizumab, a monoclonal antibody already assessed in acute polyradiculoneuropathies, and approved for myasthenia gravis. Preliminary data on eculizumab in multifocal motor neuropathy have been published, but randomized controlled studies are pending. Moreover, the neonatal Fc receptor, that recycles IgGs by preventing their lysosome degradation, is an important and attractive pharmacological target. Antibodies against FcRn, which reduce circulating IgG (both pathogenic and non-pathogenic) have been developed. The FcRn blocker efgartigimod, a humanized IgG1-derived Fc fragment, which competitively inhibits the FcRn, has recently been approved for the treatment of myasthenia gravis and is currently under investigation in CIDP. In addition, the anti-human FcRn monoclonal antibody rozanolixizumab is currently being assessed in phase 2 trials in CIDP. However, none of the abovementioned monoclonal antibodies is currently approved for treatment of any immune-mediated neuropathies. While more specific and individualized therapies are being developed, the possibility of combined treatments targeting different pathogenic mechanisms deserves consideration as well.
Topics: Antibodies, Monoclonal; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Myasthenia Gravis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Rituximab
PubMed: 35349079
DOI: 10.1007/s13311-022-01222-x -
MAbs 2015Since the commercialization of the first therapeutic monoclonal antibody product in 1986, this class of biopharmaceutical products has grown significantly so that, as of... (Review)
Review
Since the commercialization of the first therapeutic monoclonal antibody product in 1986, this class of biopharmaceutical products has grown significantly so that, as of November 10, 2014, forty-seven monoclonal antibody products have been approved in the US or Europe for the treatment of a variety of diseases, and many of these products have also been approved for other global markets. At the current approval rate of ∼ four new products per year, ∼ 70 monoclonal antibody products will be on the market by 2020, and combined world-wide sales will be nearly $125 billion.
Topics: Antibodies, Monoclonal; Drug Approval; Europe; Humans; Marketing; United States
PubMed: 25529996
DOI: 10.4161/19420862.2015.989042 -
Journal of Pharmaceutical Sciences Jan 2020Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to... (Review)
Review
Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Biological Products; Chemical Phenomena; Chemistry, Pharmaceutical; Drug Stability; Humans; Protein Stability; Stress, Mechanical
PubMed: 31465737
DOI: 10.1016/j.xphs.2019.08.009 -
Clinical Medicine (London, England) Jun 2017Monoclonal antibody therapeutics have been approved for over 30 targets and diseases, most commonly cancer. Antibodies have become the new backbone of the pharmaceutical... (Review)
Review
Monoclonal antibody therapeutics have been approved for over 30 targets and diseases, most commonly cancer. Antibodies have become the new backbone of the pharmaceutical industry, which previously relied on small molecules. Compared with small molecules, monoclonal antibodies (mAbs) have exquisite target selectivity and hence less toxicity as a result of binding other targets. The clinical value of both mAbs and ligand traps has been proven. New applications of mAbs are being tested and mAbs have now been designed to target two (bi-specific, eg TNF-α and IL-17) or more targets simultaneously, augmenting their therapeutic potential. Because of space limitations and the wide ranging scope of this review there are regrettably, but inevitably, omissions and missing citations. We have chosen to highlight the first successes in inflammatory diseases and cancer, but a broader overview of approved mAbs and related molecules can be found in Table 1.
Topics: Antibodies, Monoclonal; Biological Therapy; Humans
PubMed: 28572223
DOI: 10.7861/clinmedicine.17-3-220 -
Expert Opinion on Investigational Drugs Feb 2023Nearly a dozen monoclonal antibodies (mAbs) directed against beta-amyloid (Aβ) have been developed for the treatment of Alzheimer disease (AD), and most of these mAbs... (Review)
Review
INTRODUCTION
Nearly a dozen monoclonal antibodies (mAbs) directed against beta-amyloid (Aβ) have been developed for the treatment of Alzheimer disease (AD), and most of these mAbs are undergoing clinical trials. Newer mAbs have targeted more specific Aβ types. Lecanemab Eisai has a high affinity for large and soluble Aβ protofibrils. Data from phase 2 clinical trials have suggested the possibility of a robust efficacy signal and manageable risk of amyloid-related imaging abnormalities (ARIAs). Lecanemab is currently being studied in phase 3 trials.
AREAS COVERED
This article briefly reviews mAbs that target Aβ in AD and discusses the biology, mechanism of action, and targets of lecanemab.
EXPERT OPINION
mAbs that target Aβ are an important focus of therapeutic development for AD, with several soon to be considered for US Food and Drug Administration approval. The experience of aducanumab informs the development of other mAbs, such as lecanemab. One consideration is the conformation of Aβ targets. Targeting monomeric species has not resulted in robust clinical efficacy, whereas targeting Aβ in the form of oligomers, protofibrils, and plaques has shown evidence of slowing clinical decline. Another consideration is that mAbs will require safety monitoring for ARIAs.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Antibodies, Monoclonal; Plaque, Amyloid
PubMed: 36749830
DOI: 10.1080/13543784.2023.2178414 -
International Journal of Molecular... Aug 2022Understanding the biological mechanisms underlying the pH-dependent nature of FcRn binding, as well as the various factors influencing the affinity to FcRn, was... (Review)
Review
Understanding the biological mechanisms underlying the pH-dependent nature of FcRn binding, as well as the various factors influencing the affinity to FcRn, was concurrent with the arrival of the first recombinant IgG monoclonal antibodies (mAbs) and IgG Fc-fusion proteins in clinical practice. IgG Fc-FcRn became a central subject of interest for the development of these drugs for the comfort of patients and good clinical responses. In this review, we describe (i) mAb mutations close to and outside the FcRn binding site, increasing the affinity for FcRn at acidic pH and leading to enhanced mAb half-life and biodistribution, and (ii) mAb mutations increasing the affinity for FcRn at acidic and neutral pH, blocking FcRn binding and resulting, in vivo, in endogenous IgG degradation. Mutations modifying FcRn binding are discussed in association with pH-dependent modulation of antigen binding and (iii) anti-FcRn mAbs, two of the latest innovations in anti-FcRn mAbs leading to endogenous IgG depletion. We discuss the pharmacological effects, the biological consequences, and advantages of targeting IgG-FcRn interactions and their application in human therapeutics.
Topics: Antibodies, Monoclonal; Histocompatibility Antigens Class I; Humans; Immunoglobulin G; Receptors, Fc; Tissue Distribution
PubMed: 36077002
DOI: 10.3390/ijms23179604 -
Immunology Jan 2018Monoclonal antibody discovery and engineering is a field that has traditionally been dominated by high-throughput screening platforms (e.g. hybridomas and surface... (Review)
Review
Monoclonal antibody discovery and engineering is a field that has traditionally been dominated by high-throughput screening platforms (e.g. hybridomas and surface display). In recent years the emergence of high-throughput sequencing has made it possible to obtain large-scale information on antibody repertoire diversity. Additionally, it has now become more routine to perform high-throughput sequencing on antibody repertoires to also directly discover antibodies. In this review, we provide an overview of the progress in this field to date and show how high-throughput screening and sequencing are converging to deliver powerful new workflows for monoclonal antibody discovery and engineering.
Topics: Animals; Antibodies, Monoclonal; Drug Discovery; Genetic Engineering; High-Throughput Nucleotide Sequencing; High-Throughput Screening Assays; Humans
PubMed: 28898398
DOI: 10.1111/imm.12838