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Recombinant Antibodies
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
Melvyn Little, Sergey M. Kipriyanov
In spite of the rapid advances of the last few years, several problems such as the routine production of experimental amounts of stable recombinant antibodies from selected clones and the best means of generating high quality universal antibody libraries need to be resolved. The novel multivalent and multifunctional recombinant antibodies need to be tested in a clinical setting. Initial optimistic estimates that this technology would make hybridoma technology redundant almost overnight have now been modified. It will take somewhat longer. New perspectives, however, have already been opened for employing recombinant antibody constructs in a variety of therapeutic and diagnostic applications.
A perspective toward mass spectrometry-based de novo sequencing of endogenous antibodies
Published in mAbs, 2022
Sebastiaan C. de Graaf, Max Hoek, Sem Tamara, Albert J. R. Heck
Around the time of their initial discovery, antibodies were termed by various illustrious names, such as ‘Immunkörper’, ‘Amboceptor’, and ‘Zwischenkörper’, among many others. These terms were used more than a century ago to describe substances with antitoxin, lysin, agglutinin, and precipitin activities.12 Nowadays, the generally accepted term antibody refers to secreted immunoglobulins (Igs), whose sequence variety is several orders more diverse than the assortment of their historical names. Antibodies represent some of the most important molecules in the human immune system. Over the last century, Igs have been intensively studied because of their role in combatting infectious diseases and have taken center stage for development of therapeutics in the last decade.3–5 Beyond infectious diseases, recombinant antibodies are now also developed for cancer, rheumatoid arthritis, and various other pathological conditions.6 As key entities in the body’s defense mechanism, circulating antibodies are found in various bodily fluids, such as serum, saliva, milk, the lumen of the gut, and cerebrospinal fluid.7 New leads for biotherapeutic development of recombinant antibodies come from various sources, such as immunizing animals with specific antigens, or by discovering pathogen-neutralizing antibodies from recovered patients.8–10
Selection and characterization of FcεRI phospho-ITAM specific antibodies
Published in mAbs, 2019
Nileena Velappan, Avanika Mahajan, Leslie Naranjo, Priyanka Velappan, Nasim Andrews, Nicholas Tiee, Subhendu Chakraborti, Colin Hemez, Tiziano Gaiotto, Bridget Wilson, Andrew Bradbury
Recently, highly specific PSSAs recognizing specific-phosphorylated residues in the tau protein were generated by chicken immunization with phosphorylated peptides, followed by selection from single-chain variable fragment (scFv) libraries created from the immunized spleen and bone marrow.30 The structure of one of these antibodies was determined and showed novel complementarity-determining region (CDR) structures with a “bowl-like” conformation in CDR-H2 that tightly and specifically interacts with the phospho-Thr-231 phosphate group, as well as a long, disulfide-constrained CDR-H3 that mediates peptide recognition.14 The success of this strategy has led to production of additional PSSAs to other phosphorylation sites based upon screening of specifically designed scFv libraries.31 The antibodies obtained using these methods31 showed phospho-peptide specificity, but required prior target protein immunoprecipitation to demonstrate recognition of phosphorylation sites in proteins on western blots. While the low affinity of these new reagents has been a limitation to date, recombinant antibodies can be modified by invitro evolution to improve affinity or specificity.32 Furthermore, reproducibility is a hallmark of recombinant probes. In general, two reduced-size antibody formats, scFvs33 and antigen-binding fragments (Fabs), both of which comprise the essential antibody binding portions, are used in invitro display systems.
The antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy
Published in Expert Review of Anti-infective Therapy, 2022
Shan Su, Haiying Yan, Li Min, Hongmei Wang, Xueqi Chen, Jinyi Shi, Shujuan Sun
Antibody-based therapeutics have come of age, with advances in the genetic engineering of recombinant antibodies allowing application of the growing body of knowledge of the immunopathology of diseases to the development of novel drugs. Antifungal antibodies could provide long-awaited novel therapies for use in combination with antifungal agents. Efungumab is a genetically recombinant antibody against fungal heat shock protein 90 (hsp90), which has become a mainstay in combination therapy. The in vitro activity of efungumab combined with caspofungin was tested. It demonstrated synergy with C. albicans, C. glabrata, C. parapsilosis and C. lusitaniae [103]. The MIC of efungumab was reduced from 128 µg/mL-256 µg/mL to 8–32 µg/mL, the MIC of caspofungin was reduced from 0.25–2 µg/mL to 0.12–0.5 µg/mL, and the FICI was 0.31–0.37 [104]. These data were further exhibited in the mouse model. The combination of efungumab with caspofungin exhibited statistically significant higher fungal inhibition than caspofungin monotherapy based on tissue biopsies from Candida spp.-infected mice (P < 0.5) [103]. We hypothesize that the antifungal activities of other antibodies could be explored to develop novel antifungals. A study showed that Hsp90 is required for azole and echinocandin resistance in Aspergillus fumigatus (A. fumigatus), and the repression of Hsp90 reduced A. fumigatus virulence and potentiated the effect of the echinocandin caspofungin [105]. Further research is needed to determine the synergistic mechanism of efungumab in combination with caspofungin against Candida species.