Immunological Tests for Diagnosis of Disease and Identification of Molecules
Julius P. Kreier in 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).
Laboratory Procedures and Management
Jeremy R. Jass in Understanding Pathology, 2020
Antibodies can be raised artificially by injecting antigenic material into an animal. To achieve production of a specific antibody of a single type that recognises only a single antigen would require difficult purification that would yield very little antibody. Koehler and Milstein (1975) developed a technique for producing very large amounts of monoclonal antibody and their efforts were rewarded with a Nobel prize. Their technique involved the fusion of primed B lymphocytes (obtained from a mouse that had previously been injected with antigen) with malignant and therefore immortal plasma cells. The resulting hybrid cell engineered in the laboratory contained both the specific instruction as well as the machinery to produce antibody. Furthermore, one could begin with a single cell which would divide and produce identical cells (a hybridoma) all secreting the same monoclonal antibody.
Treatment of Patients with Rheumatoid Arthritis with Anti-CD4 Monoclonal Antibodies
Thomas F. Kresina in Monoclonal Antibodies, Cytokines, and Arthritis, 2020
None of the eight patients developed severe side effects to the monoclonal antibody treatment. Only patient 4 had low-grade fever for 1 day. As shown in Fig. 1, significant improvement in the clinical variables of morning stiffness (mean 59%), pain assessment (74%), and Ritchie articular index (70%) occurred in all eight patients within 1 week after initiation of therapy. Follow-up examination of these clinical parameters after 16 weeks showed stabilization of the underlying disease in some patients. The amelioration lasted in patient 2 for 5½ months, in patient 3 for 8 months, and in patients 5, 6, and 8 for > 12 months. Clinical improvement in patient 1 lasted only for 3 weeks; nevertheless, a dramatic improvement of a vasculitis in the right thumb could be noted. Patient 4 felt better for only about 8 weeks. Patient 7 showed in general only marginal improvement of clinical symptoms. No difference in efficacy between VIT4 and MT151 treatment was observed (patients 1–3 were treated with VIT 4 and patients 4–8 with MT151).
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
Monoclonal antibodies are a type of passive immunotherapy that could be an effective therapeutic intervention against a specific disease [8]. A monoclonal antibody is a laboratory-created molecule that mimics or improves the body's natural immune response to an invader, such as tumors or infections. Since monoclonal antibodies are engineered to target an important portion of the infectious process directly, they offer an advantage over conventional methods of antiviral treatment. A monoclonal antibody is made by exposing a white blood cell to a specific viral protein and cloning it to mass generate antibodies against a particular virus. Monoclonal antibodies have been developed even before the COVID-19 pandemic, where they are used to treat various viral illnesses, including Ebola and rabies [9]. Since SARS-CoV-2 utilizes its spike protein to bind to the ACE2 receptors to enter human cells, various neutralizing monoclonal antibodies have been produced that target the spike protein in an attempt to prevent the virus from infecting human cells [10].
Effective suppression of tumour cells by oligoclonal HER2-targeted delivery of liposomal doxorubicin
Published in Journal of Liposome Research, 2019
Alireza Farasat, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Saeed Ranjbar, Shahryar Khoshtinat Nikkhoi
Despite the extensive success of monoclonal antibody-based treatment in the past two decades, the often modest response to these therapies inspires the development of optimal drug combinations and improved therapeutics. Early attempts of designing novel approaches to target specific antigens, including monoclonal antibody (mAb) combinations (Sym004; bi-clonal), dual-specific antibodies (MEHD7945a) and ADCC-enhanced antibodies (imgatuzumab), have failed to show enhanced clinical activity. As previously shown by Drebin et al., the strategy of combining two or more mAbs against distinct epitopes of the same receptor may improve the efficiency of mAbs (Drebin et al.1988; Kasprzyk et al.1992). Previous studies have attributed this enhanced activity to several factors, which generally lead to increased immune effector cell-mediated cytotoxicity.
Selection of bispecific antibodies with optimal developability using FcRn‑Ph‑HPLC as an optimized FcRn affinity chromatography method
Published in mAbs, 2023
Thomas Müller, Carolin Tasser, Michael Tesar, Ivica Fucek, Ute Schniegler-Mattox, Joachim Koch, Kristina Ellwanger
Monoclonal antibody (mAb)-based therapeutics are a vital treatment strategy for patients with various diseases.1 Among these, bispecific antibodies (bsAbs) are a growing class of antitumor therapeutics that can target two antigens simultaneously, enabling novel mechanisms of action inaccessible to standard mAbs.2 These novel mechanisms include the recruitment of innate and adaptive immune cells to tumor sites for the induction of anti-tumor antibody-dependent cellular cytotoxicity (ADCC),3–5 and dual targeting of tumor-associated antigens.6 The efficacy, method of administration and dosing-regimen of IgG-based antibody therapeutics are heavily reliant on their serum half-life and their pharmacokinetic (PK) properties.7 A persistent challenge in the preclinical characterization of IgG therapeutics is the identification of drug candidates that are most likely to exhibit the optimal PK required to elicit the greatest response and most convenient dosing strategy in patients with a particular disease.8 Methods to accurately predict and monitor half-life and other PK properties are needed to identify IgG therapeutics with the greatest developability and feasibility for clinical use early in the drug discovery process.7,9
Related Knowledge Centers
- Antibody
- Bispecific Monoclonal Antibody
- Cloning
- Polyclonal Antibodies
- White Blood Cell
- Epitope
- Plasma Cell
- Lineage
- Monoclonality
- Antigen