Cancer immunotherapy targeting carbohydrate antigens

Cancer immunotherapy aims to harness the immune system to fight cancer. Cancer cells harbor diverse modifications that lead to neoantigens, including aberrant expression of cell surface carbohydrates. Targeting tumor-associated carbohydrate antigens (TACA) holds great potential for cancer immunotherapy. Here we designed an active cancer vaccine immunotherapy strategy to target TACA-positive tumors. We generated biomimetic glyconanoparticles to form nano-ghosts (NG) that either express (NG^pos) or lack expression (NG^neg) of TACA-glycoconjugates in their natural context. We show that optimized immunization of mice with NG^pos glyconanoparticles induce a strong, diverse and persistent anti-Neu5Gc IgG immune response, in contrast to the control NG^neg. Resulting anti-TACA IgG were also detected within Neu5Gc-positive tumors and inhibited tumor growth in-vivo. Using detailed glycan microarray analysis, we further demonstrate that the kinetics and quality of the immune response has a major influence on the efficacy of the therapeutic cancer vaccine. Combination therapy of this cancer vaccine together with checkpoint inhibitors therapy was even more effective then each of the individual treatments. These findings reinforce the potential of TACA neoantigens as immunotherapy targets.