Merck, MABF2069, Anti-Glucuronoxylomannan (GXM) Antibody, clone 18B7

Cryptococcus neoformans is an encapsulated yeast-like fungus that is reported to causes systemic infections, including fatal meningoencephalitis. Glucuronoxylomannan (GXM) is the principal constituent of the Cryptococcus neoformans capsule that modulates the inflammatory response of human monocytes in vitro. The basic structural unit of GXM is a tri-mannose repeat with a glucuronic acid residue in the first mannose. Its structure is shown to be further modified in individual strains by the addition of xylose substitutions on the mannan backbone. Six triads known as M1-M2 are shown to be present in various proportions in GXM from the various serotypes and M2 is reported to be the most common triad in serotype A GXM. Soluble GXM serves as an important virulence factor and contributes to the pathogenesis of infection, and high levels of GXM have been found in serum of patients with cryptococcosis. Clone 18B7 displays significant activity against GXM and is reported act by possibly hydrolyzing the oligosaccharide substrate. This antibody acts as a potent opsonin for Cryptococcus neoforman by increasing its phagocytosis. This antibody may also reduce GXM levels by interfering with the release of polysaccharide from the capsule. Administration of this antibody to mice is shown to rapidly clear serum Cryptococcal antigen. (Ref.: Bowen, A., et al. (2017). J. Biol. Chem. 292(2); 417-434; Martinez, LR., et al. (2004). Infect. Immun. 72(6); 3674 3679; Tissi, L., et al. (2004). Infect. Immun. 72(11); 6367-6372; Devi, SJN et al. (1991). Infect. Immun. 59(10); 3700-3707).