Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy

Figure 2

Schematic representation of the main pathway of O-acetyl-GD2 ganglioside biosynthesis. GD2 ganglioside is synthesized by the action of N-acetyl-galactosyltransferase I, which transfers N-acetyl-galactosaminyl residue from UDP-N-acetyl-galactosamine to GD3 [66]. GD2 can be also formed by the action of alpha 2–8 sialyltransferase II, which transfers a sialic acid residue from CMP-sialic acid to GM2 [66]. After synthesis, GD2 can be converted into either GD1b or GT2. GD1b is formed by the action of galactosyltransferase II that transfers a galactose residue from UDP-galactose to GD2. GT2 is synthesized by the action of sialyltransferase III that transfers a sialic acid residue from CMP-sialic acid to GD2. Then, the O-acetyl group addition occurs in a postsynthetic fashion [66]. Thus, O-acetyl-GD2 can be synthesized either by the action of sialate-O-acetyltransferase, which transfers the O-acetyl group to GD2, or by the action of N-acetyl-galactosyltransferase I, which transfers N-acetyl-galactosaminyl residue from UDP-N-acetyl-galactosamine to O-acetyl-GD3. Cer, ceramide; GlcCer, glucosylceramide; LacCer, lactosylceramide; Gal, galactose; Glc, glucose; GalNAc, N-acetylgalactosamine; Neu5Ac, N-acetylneuraminic acid; Glc T, glucosyltransferase; Gal T, galactosyltransferase; ST, sialyltransferase; GalNacT, N-acetyl-galactosaminyltransferase; CASD 1, Cas 1 domain containing 9(7)-O-acetyl transferase.