Journal: Antibodies

Abbreviation

Antibodies (Basel)

Publisher

MDPI

Journal Volumes

ISSN

2073-4468

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20153
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Publications 1 - 3 of 3
  • What makes a bacterial oral vaccine a strong inducer of high-affinity IgA responses?
    Item type: Review Article
    Moor, Kathrin; Slack, Emma (2015)
    Antibodies
    Oral vaccination against bacterial pathogens that infect via the gastrointestinal tract is highly desirable for both economic reasons and the supposed benefits of local mucosal immunity. However, the majority of oral vaccine trials in humans result in failure. Here we try to assimilate our current knowledge to generate a model to improve vaccine development strategies. A model previously postulated describes the “immunogenicity” of intestinal bacterial species as a sum of the ability of the species to compete with the microbiota, the “pathogenicity index,” and the uniqueness of the species. While this model quite neatly explains the difficulties in generating appropriately attenuated live vaccine strains, it cannot explain the success of fully apathogenic or inactivated high-dose vaccines. We therefore propose a step away from focusing on bacterial traits, and towards the most basic requirements of mucosal vaccines: i.e., the delivery of antigen to the gut-associated lymphoid tissues and the ability of that antigen to induce germinal center formation. While the models seem trivial, both suggest that vaccination strategies permitting uncoupling of disease-causing phenomena from immune stimulation will have a much broader safety margin in a diverse human population. Our modified model further suggests the benefits of delivering antigen in the form of high-dose fully apathogenic or sterile particles, combined with relevant adjuvants.
  • Antibody conjugates: from heterogeneous populations to defined reagents
    Item type: Review Article
    Dennler, Patrick; Fischer, Eliane; Schibli, Roger (2015)
    Antibodies
    Monoclonal antibodies (mAbs) and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal therapeutic efficacy, immunoglobulins are conjugated with toxic payloads to form antibody drug conjugates (ADCs) and with chelating systems bearing therapeutic radioisotopes to form radioimmunoconjugates (RICs). Besides their therapeutic applications, antibody conjugates are also extensively used for many in vitro assays. A broad variety of methods to functionalize antibodies with various payloads are currently available. The decision as to which conjugation method to use strongly depends on the final purpose of the antibody conjugate. Classical conjugation via amino acid residues is still the most common method to produce antibody conjugates and is suitable for most in vitro applications. In recent years, however, it has become evident that antibody conjugates, which are generated via site-specific conjugation techniques, possess distinct advantages with regard to in vivo properties. Here, we give a comprehensive overview on existing and emerging strategies for the production of covalent and non-covalent antibody conjugates.
  • A Monoclonal Antibody to Human DLK1 Reveals Differential Expression in Cancer and Absence in Healthy Tissues
    Item type: Journal Article
    Bujak, Emil; Ritz, Danilo; Neri, Dario (2015)
    Antibodies
    There is considerable interest in the characterization of novel tumor-associated antigens that lend themselves to antibody-mediated pharmacodelivery strategies. Delta-like 1 homolog protein (DLK1), which exists both as transmembrane protein and in soluble form, shows a restricted pattern of expression in healthy organs, while being overexpressed in some tumors. We have generated a human antibody specific to DLK1 using phage display technology. This reagent was used for a comprehensive characterization of DLK1 expression in freshly frozen sections of normal human adult tissues and of xenografted human tumors. DLK1 was virtually undetectable in most organs, except for placenta which was weakly positive. By contrast, DLK1 exhibited a moderate-to-strong expression in 8/9 tumor types tested. Our analysis shed light on previous conflicting reports on DLK1 expression in health and disease. The study suggests that DLK1 may be considered as a target for antibody-mediated pharmacodelivery strategies, in view of the protein’s limited expression in normal tissues and its abundance in the interstitium of neoplastic lesions
Publications 1 - 3 of 3