Conversion of Tumors into Autologous Vaccines by Intratumoral Injection of -Gal Glycolipids that Induce Anti-Gal/-Gal Epitope Interaction
Figure 1
(a) Ceramide decahexoside as a representative α-gal glycolipid. This glycolipid has 10 carbohydrate branched chain. The α-gal epitope (Galα1-3Galβ1-4GlcNAc-R) marked by the broken line rectangles caps both carbohydrate branches. The terminal α-galactosyl (Gal) unit is linked α1,3 to the penultimate Gal of the carbohydrate chain by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT). The lipid portion of α-gal glycolipids (ceramide) anchors the carbohydrate portion in the cell membrane via the two fatty acid tails. (b) Anti-Gal-mediated targeting of tumor cells to APC in lesions injected with α-gal glycolipids. Intratumoral injection of α-gal glycolipids results in insertion of these glycolipids in tumor cell membranes. Anti-Gal IgG binds in situ to α-gal epitopes on the inserted glycolipids. Subsequent interaction between the Fc portion of the bound anti-Gal and FcγR on the APC (illustrated as a dendritic cell) induces uptake of intact or lysed tumor cells by APC, resulting in effective internalization of the tumor-associated antigens (TAA). Internalized TAA are processed and various immunogenic TAA peptides (⚫, ■, ▲) are presented by the APC in association with class I and class II MHC molecules. These immunogenic peptides can activate tumor specific cytotoxic and helper T cells and elicit a protective antitumor immune response.
