Synthesis and Evaluation of Liposomal Anti-GM3 Cancer Vaccine Candidates Covalently and Noncovalently Adjuvanted by αGalCer

GM3,
a typical tumor-associated carbohydrate antigen, is considered
as an important target for cancer vaccine development, but its low
immunogenicity limits its application. αGalCer, an iNKT cell
agonist, has been employed as an adjuvant via a unique immune mode.
Herein, we prepared and investigated two types of antitumor vaccine
candidates: (a) self-adjuvanting vaccine GM3-αGalCer by conjugating GM3 with αGalCer and (b) noncovalent vaccine GM3-lipid/αGalCer, in which GM3 is linked with lipid
anchor and coassembled with αGalCer. This demonstrated that
βGalCer is an exceptionally optimized lipid anchor, which enables
the noncovalent vaccine candidate GM3-βGalCer/αGalCer to evoke a comparable antibody level to GM3-αGalCer. However, the antibodies induced by GM3-αGalCer are better at recognition B16F10 cancer cells and more effectively
activate the complement system. Our study highlights the importance
of vaccine constructs utilizing covalent or noncovalent assembly between
αGalCer with carbohydrate antigens and choosing an appropriate
lipid anchor for use in noncovalent vaccine formulation.