A Biomimetic Self-Adjuvanting Glycoprotein Vaccine Platform Elicits Potent Antitumor Immunity against GD2-Positive Cancers

The inherently low immunogenicity of tumor-associated carbohydrate antigens poses a significant obstacle to effective cancer immunotherapy. To address this challenge, we here report a biomimetic self-adjuvanting glycoprotein vaccine platform to elicit robust antitumor immunity against disialoganglioside GD2-positive cancers. This platform is constructed through the site-specific conjugation of a TLR4 agonist GAP112 (MPLA adjuvant analogue) to a carrier protein that is loaded with a chemoenzymatically synthesized GD2 glycan antigen. This precisely engineered "adjuvant-protein-antigen" conjugate is further incorporated into a biomimetic liposomal formulation to enhance its delivery and immune response. The resulting vaccine significantly enhanced lymph node migration and promoted both antigen uptake and maturation of antigen-presenting cells (APCs). Crucially, our vaccine elicited a potent GD2-specific IgG antibody response with markedly higher titers than those from an unconjugated mixture. Sera from immunized mice effectively bound to the target tumor cells and mediated potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), demonstrating functional antitumor immunity. This versatile platform presents a powerful strategy for developing robust carbohydrate-based cancer vaccines, holding substantial promise for broad application in cancer immunotherapy.