Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database

Abstract

Antibodies are used extensively for a wide range of basic research and clinical applications. While an abundant and diverse collection of antibodies to protein antigens have been developed, good monoclonal antibodies to carbohydrates are much less common. Moreover, it can be difficult to determine if a particular antibody has the appropriate specificity, which antibody is best suited for a given application, and where to obtain that antibody. Herein, we provide an overview of the current state of the field, discuss challenges for selecting and using antiglycan antibodies, and summarize deficiencies in the existing repertoire of antiglycan antibodies. This perspective was enabled by collecting information from publications, databases, and commercial entities and assembling it into a single database, referred to as the Database of Anti-Glycan Reagents (DAGR). DAGR is a publicly available, comprehensive resource for anticarbohydrate antibodies, their applications, availability, and quality.

Targeting cancer-specific glycans by cyclic peptide lectinomimics

“…Significant efforts have been undertaken to produce glycan-specific antibodies (Dalziel et al 2014; Fuster and Esko 2005) However, these have been difficult, as glycans are poor immunogens often resulting in weak affinity IgM antibodies with limited clinical value and low specificity of existing antibodies (Pinho and Reis 2015; Sterner et al 2016) One of the most promising and the most widely explored tumor-associated glycan structures in many diagnostic and (immuno)therapeutic approaches are truncated mucin-type O -glycans such as Tn (αGalNAc-Thr/Ser), sTn (αNeu5Ac-(2,6)-αGalNAc-Thr/Ser), and T (Galβ1-3GalNAcα1- O -Ser/Thr) (Cazet et al 2010) The major protein carrier of these tumor-associated glycans is the MUC1 glycoprotein, highly expressed in a variety of epithelial cancers, but absent from normal tissues (Nath and Mukherjee 2014) Despite the great potential, the generation of clinically relevant human antibodies with good affinity and specificity for tumor-associated glycans of MUC1 proves to be a challenging task (Loureiro et al 2015; Feng et al 2016) Identification of MUC1 glycan/peptide epitopes within a MUC1 tandem repeat, which are able to overcome immunological self-tolerance and yet induce stronger and long-lasting immune response is the current focus of immunotherapy approaches (McDonald et al 2015; Hossain and Wall 2016) An excellent example of such approaches is the PankoMab-GEX, a humanized monoclonal antibody that binds to a novel carbohydrate-induced conformational epitope on MUC1 (glycopeptide epitope) with a high affinity, which is currently undergoing clinical trials for ovarian cancer (Fiedler et al 2016)…”

Glycosylation of extracellular vesicles: current knowledge, tools and clinical perspectives

“…However, whereby antibodies are the best-in-class reagents for protein recognition, their applicability to the study of glycosylation is diminished. Antibodies against N-glycans recognise families of related glycan structures as opposed to specific epitopes and monoclonal N-glycan antibodies are also exceedingly rare [73]. Indeed, in a recently compiled database of anti-glycan reagents only 25 of a total 1116 entries correspond to N-glycan antibodies [73].…”

Inhibition of N-Glycosylation towards Novel Anti-Cancer Chemotherapeutics

“…Furthermore, abnormal glycosylation of cell surface proteins takes place during which normal cells progress to a malignant neoplastic state [1]. Thus, the modification of cell surface glycosylation is a characteristic of many cancer cells [2–4].…”

“…Many of the recently developed tumor markers are carbohydrate antigens. Identification of cell type-specific or tissue-specific glycoconjugates (tumor markers) has lead to the discovery of new assay systems or diagnosis for certain cancers via immunodetection reagents [1]. On the other hand, anti-glycan antibodies have a limited application for cancer treatment, despite the fact that a great number of tumor-associated glycans have been identified with the help of modern glycomic approaches [6].…”

“…In the last two decades, a few monoclonal antibodies targeting ganglioside GD 2 or GD 3 and a cancer vaccine with N -glycolylated ganglioside GM 3 have been developed into clinical trials. As such, changes and diversification of the expression profile of cell surface glycans based on the underlying glycobiology have received much attention from the scientific community [1]. Two of the most abundant forms of glycosylation occurring on proteins destined to be secreted or membrane-bound proteins are N -linked (to Asp (N), N -glycosylation) and mucin-type O -linked (to Ser/Thr, O -glycosylation).…”