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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
The high specificity of monoclonal antibodies for antigens has led to their development as precision therapeutics to block protein interactions, prevent receptor signalling, or label their targets for destruction. Antibody-based therapies are now the dominant class of biopharmaceuticals and are used to treat a variety of diseases. When new therapeutic targets are identified, antibodies can provide a rapid route to modifying their functions. Monoclonal antibody treatments have proved particularly effective in the treatment of rheumatoid arthritis, where the inflammatory cytokines TNF-alpha and IL-6 are important mediators of disease pathogenesis. Biologic disease-modifying antirheumatic drugs include monoclonal antibodies specific for TNF-alpha, IL-6 and the receptor for IL-6 (see Chapter 4, Rheumatic disease). Recombinant proteins can also be used as therapeutics. For example, the drug anakinra is a modified form of the IL-1 receptor antagonist used for the treatment of rheumatoid arthritis. Disadvantages of such therapies include their high cost and potential to increase susceptibility to infections such as tuberculosis.
Immunological Tests for Diagnosis of Disease and Identification of Molecules
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
A monoclonal antibody is an antibody secreted by cells of the clones of a single lymphocyte isolated from an experimental animal. Monoclonal antibodies are highly specific because they consist of antibody specific to a single epitope. Monoclonal antibodies are produced by cell hybrids which are made in the laboratory by fusing antibody-secreting cells with immortal cancer cells. In a typical process, a mouse is first immunized with the antigen of interest, then its antibody-producing cells are removed usually from the spleen and fused with mouse cancer cells. The cancer cells impart immortality to the fusion product, the hybridorna, and the spleen cell partner provides the ability to produce and secrete antibodies. The hybridomas are separated into single clones and screened for antibody production. The clones that produce the desired antibodies are retained, and the antibodies are mass-produced and purified (Figure 20.17).
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Since disclosure of the murine hybridoma technology by Milstein and Koehler in 1975, there has been remarkable progress in the use of antibodies to treat a range of diseases, including cancer. This is reflected in the financial analyses for antibody therapies; for example, the global monoclonal antibodies (mAbs) market was valued at $85.4 billion in 2015 and is expected to reach a value of at least $138.6 billion by 2024. Increasing demand for agents for use in precision medicine scenarios (Chapter 11) is an important factor responsible for the growing effort to develop therapeutic antibodies as targeted therapies for individual patients. Furthermore, antibody therapies offer the hope of fewer adverse effects due to their exquisite selectivity. Single agent (or “naked”) antibodies represent the largest sub-family of antibody-based therapies at present, with well-known examples including trastuzumab (HerceptinTM) and bevacizumab (AvastinTM). However, Antibody-Drug Conjugates are a fast-growing area expected to reach a market value of ~$10.0 billion by 2025, and bispecific antibody technologies are growing at a similar rate.
Long-acting injectable formulation technologies: challenges and opportunities for the delivery of fragile molecules
Published in Expert Opinion on Drug Delivery, 2022
Andrea Gonella, Sylvestre Grizot, Fang Liu, Adolfo López Noriega, Joël Richard
The growing interest around the use of peptide therapeutics is well documented by the huge number of molecules in active clinical development, estimated to be around 170, covering a wide range of applications. Considering only approved molecules, areas such as urology, respiratory, and cardiovascular diseases, pain, oncology, metabolic disorders, and infections are most commonly associated to peptide drugs treatments [6]. Regarding protein therapeutics, monoclonal antibody-based therapies have had incredible success over the last decades, due to the high specificity and usually long half-life of these molecules. Monoclonal antibodies found many applications for indications such as cancer (e.g. Trastuzumab or Bevacizumab) or immune diseases (e.g. Adalimumab or Infliximab). However, many other protein therapeutics like hormones, cytokines, growth factors, and enzymes, were approved in the past and are currently used for the treatment of many diseases (e.g. multiple sclerosis, Gaucher’s disease or rheumatoid arthritis) [7,8].
The use of neutralizing monoclonal antibodies and risk of hospital admission and mortality in patients with COVID-19: a systematic review and meta-analysis of randomized trials
Published in Immunopharmacology and Immunotoxicology, 2022
Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan
The safety of these neutralizing monoclonal antibodies can be a concern since they are newly approved agents with limited clinical experience of use. We observed that infusion-related reactions were reported more frequently among patients in the intervention group than the control group in the majority of the included trials [13–16,18,19]. In the trial by Chen et al. [13], the authors reported that most of these events which occurred during the infusion, including pruritus, flushing, rash, and facial swelling, were reported as mild in severity. In the trial by Gupta et al. [17], one patient receiving sotrovimab had an infusion-related reaction (moderate dyspnea) that was considered related to study treatment. In the trial by Gottlieb et al. [14], immediate hypersensitivity reactions that could have been infusion-related were reported as mild in severity and not dose-related, including pruritus, flushing, rash, and facial swelling. The other included trials did not describe in detail the nature of infusion-related reactions.
Nanovesicles released by OKT3 hybridoma express fully active antibodies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Mariantonia Logozzi, Rossella Di Raimo, Francesca Properzi, Stefano Barca, Daniela F. Angelini, Davide Mizzoni, Mario Falchi, Luca Battistini, Stefano Fais
Antibody-based therapies are gaining increasing interest in medicine and they are paving the way for modern immunotherapy. Monoclonal antibodies are used against various diseases, including cancer and autoimmune diseases. Monoclonal antibodies-mediated therapies are an example of direct targeting therapy and they aim at curing diseases by binding disease-associated epitopes, recognised by monoclonal antibodies. However, despite the promising results, clinical application is limited due to (i) the high costs hardly sustainable for the public healthcare systems, (ii) the critical level of toxicity53, frequently leading to the interruption of therapies and (iii) unfortunately a low level of efficacy probably due to an unexpected low specificity of the antibodies. More research is needed to identify better formulations allowing a better clinical efficacy of therapeutic antibodies, together with a reduced level of systemic toxicity.