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Overview of Cell Adhesion Molecules and Their Antagonism
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
There are several methods by which adhesion molecule function might be inhibited (Fig. 3). The most direct strategy involves specific inhibition of the adhesion molecule or its counter-receptor. This has been the method used most widely in both animal models of inflammation as well as in the few human studies using antiadhesion therapy (8,28). Most studies have utilized monoclonal antibodies (mAb) as the therapeutic agent. Monoclonal antibodies possess several desirable characteristics, including exquisite target specificity, availability in large quantities, and the ability to execute various effector functions via their Fc receptors. However, as most mAb produced to date have been generated in mice, there are potential limitations to their therapeutic use for human disease. Because they are foreign, murine mAb will elicit human anti-mouse antibody (HAMA) responses. On repeated administration, these HAMA may not only decrease the serum half-life and thereby the therapeutic utility of the mAb but may also cause potentially serious adverse effects. To circumvent these problems, several methods to reduce the immunogenicity of therapeutic mAb have been developed. Utilizing the techniques of molecular biology, researchers can substitute parts of human antibodies for the murine, yielding chimeric and humanized mAbs (28). The most eagerly awaited development is the ability to produce human mAbs directed against targets such as adhesion receptors.
The Immunogenicity of Foreign Monoclonal Antibodies in Human Disease Applications: Problems and Current Approaches
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
The initial reports describing the immunogenicity of antibodies in humans were concerned primarily with murine mAbs. The resulting immune response was therefore referred to as “Human Anti-Mouse Antibody” or HAMA. This term has gained widespread acceptance among immunologists. In recent years, however, antibodies of various species, including human, have been tested in clinical trials. Therefore, in this review I will use the more general term “Human Antiimmunoglobulin Response”, or human anti-Ig, when referring to the immunogenicity of various types and species of antibodies in humans.
The science of biotechnology
Published in Ronald P. Evens, Biotechnology, 2020
Figure 5.7 presents the molecular engineering for the humanization of murine mab molecules in three possible ways. The first change is listed as #1 in the figure, “chimeras,” and involves only changes in the CDRs responsible for target/antigen binding [30% human, 70% murine molecule]. The second change is listed as #2 in the figure, “Humanized” forms [90% humanized]. The third change is listed as #3 in the figure, “human” mabs [100% human]. The goals of humanization are reducing or eliminating the human anti-mouse antibody rejection of murine mabs, less adverse effects from mouse antigens, improved affinity of the mabs (CDRs) to target cell surface antigens, and improved mab mechanisms of action for cytotoxicity (both antigen-dependent and complement-dependent types, ADCC and CDCC, respectively, at the CH3 Fc segment of the mab). Over 95% of mabs are humanized to some extent.
Comparison of a new enzymatic assay for serum homocysteine on Toshiba TBA-c16000 against an immunoassay on Abbott Architect
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
Prior to the development of mouse monoclonal antibodies, immunoassays were not the mainstream detection methods for Hcy analysis. Frantzen et al. introduced the technique of employing a monoclonal mouse anti-SAH antibody to measure the amount of SAH in a competitive enzyme immunoassay [17]. Without the use of radioisotopes and tedious chromatographic separation, this method allowed the development of an automated platform for Hcy analysis. The precision and correlation values of HPLC were acceptable. In addition, a fluorescence polarization immunoassay has been developed [18] and can be performed using an Abbott IMX analyzer (Abbott Park, IL). These methods facilitated the commercialization of Hcy assays, as most clinical laboratories have such equipment necessary to perform immunoassays. The use of a monoclonal antibody is the key to immunoassays, but it is also responsible for a major limitation of immunoassays due to additional antibody interactions in serum from patients receiving human anti-mouse antibody therapy or in those with heterophilic antibodies [19,20].
A promising cancer diagnosis and treatment strategy: targeted cancer therapy and imaging based on antibody fragment
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Xuhong Zhao, Qian Ning, Zhongcheng Mo, Shengsong Tang
As a natural ligand with high specificity and affinity, antibody is one of the main research objects in targeted tumour therapy and imaging. Monoclonal antibody (mAb) is first-generation antibody drugs, and also produces exciting results in the treatment of solid tumours and haematological malignancies [8–10]. In view of the outstanding therapeutic effect of mAb, the investment of antibody drug research and development is rapidly increased. Significantly, the Food and Drug Administration (FDA) has approved the clinical application of several mAbs, such as bevacizumab, ipilimumab and trastuzumab [11–13]. However, after long-term clinical application and research, the defects of mAb have been gradually discovered. One major impediment is that murine mAb entering the human body cause a human anti-mouse antibody (HAMA) response [14]. The HAMA response causes a strong allergic reaction and rapidly eliminates mAb in vivo resulting poor tumour uptake. Although it is feasible to alleviate the murine problem of mAbs through grafting the complementarity determining regions (CDR) of mouse antibody in human immunoglobulins, the mAb still have limitations of large volume (four polypeptide chains) and long half-life [15,16].
S3Ab, a novel antibody targeting B lymphocytes, is a potential therapeutic agent for B-lineage malignancies
Published in Journal of Drug Targeting, 2019
Sisi Li, Hongqiang Shen, Qiang Shu
In conclusion, we believe that S3Ab can be an excellent antibody in targeting treatment in B cell-derived lymphoid cancer and B-cell-dependent autoimmunity. The DNA sequences of S3Ab and CD79α extracellular segment sequence recognised by S3 antibody have been recently identified. Nowadays, we mainly focus on genetic engineering to reduce the potential side effects of the human anti-mouse antibody (HAMA) in clinical applications. The aim of our team is to make a CAR-T cell based on S3 antibody.