Abstract:
The present disclosure relates to glycoproteins, particularly monoclonal antibodies, comprising a glycoengineered Fc region, wherein said Fc region comprises an optimized N-glycan having the structure of Sia2(α2-6)Gal2GlcNAc2Man3GlcNAc2. The glycoengineered Fc region binds FcγRIIA or FcγRIIIA with a greater affinity, relative to comparable monoclonal antibodies comprising the wild-type Fc region. The monoclonal antibodies of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, autoimmune, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
Abstract:
The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycans and glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.
Abstract:
A novel UDP-Gal regeneration process and its combined use with a galactosyltransferase to add galactose to a suitable acceptor substrate. Also described herein are synthetic methods for generating Globo-series oligosaccharides in large scale, wherein the methods may involve the combination of a glycosyltransferase reaction and a nucleotide sugar regeneration process.
Abstract:
Described herein are synthetic glycan conjugates comprising a carrier and a glycan moiety derived from Neisseria meningitidis, wherein the glycan moiety is covalently linked to the carrier through a linker. Also provided herein are a mixture of the glycan conjugates thereof, immunogenic compositions thereof, and kits thereof. The invention further provides methods of using the synthetic glycan conjugates and immunogenic compositions thereof to treat and/or reduce the risk of infectious diseases such as bacterial infections.
Abstract:
Immunogenic compositions, cancer vaccines and methods for treating cancer comprising FMS, the fucose-enriched polysaccharide fraction from Reishi F3, are provided. Compositions comprise fucose-enriched Reishi polysaccharide fraction (FMS) MW=˜35 kDa, wherein the FMS is isolated by size-exclusion chromatography from Reishi F3, and the FMS comprises polysaccharides having primarily a backbone selected from 1,4-mannan and 1,6-α-galactan, wherein the backbone is linked to a terminal fucose-containing side-chain Immunogenic compositions comprising glycolipid adjuvants are provided. Antibodies generated by immunogenic compositions disclosed herein bind cancer cells comprising antigens Globo H, Globo H, Gb3, Gb4, Gb5 (SSEA-3) and SSEA-4 on the cell surface.