Active cancer vaccine targeting carbohydrates for immunotherapy

Abstract

Abstract Transformed cells present cell surface neoantigens, including aberrantly expressed carbohydrates. Targeting tumor-associated carbohydrate antigens could be useful for cancer immunotherapy. N-glycolylneuraminic acid (Neu5Gc) is a non-human carbohydrate consumed in diet and accumulates on human cancer cells, leading to expression of neoantigens. Passive immunotherapy with anti-Neu5Gc antibodies in mice inhibits tumor growth. Here we describe an active cancer vaccination immunotherapy strategy to target Neu5Gc-positive tumors. We generated glyconanoparticles from engineered red blood cells to form nano-ghosts (NGs) that either express (NGpos) or lack expression (NGneg) of Neu5Gc-glycoconjugates. We then show that optimized immunization of Neu5Gc-deficient Cmah-KO mice with NGpos glyconanoparticles induce a robust, diverse and long-lasting anti- Neu5Gc IgG immune response. Anti-Neu5Gc IgG antibodies also migrated into Neu5Gc-positive tumors and inhibited tumor growth in-vivo. Using glycan microarrays we also show that the kinetics and quality of the immune responses influence the efficacy of the vaccine. Hence, immunotherapy targeting Neu5Gc-carbohydrate neoantigens is promising.