Fully Synthetic TF-Based Self-Adjuvanting Vaccine Simultaneously Triggers iNKT Cells and Mincle and Protects Mice against Tumor Development

The Thomsen–Friedenreich (TF) antigen has proven
to be a
promising target for developing novel therapeutic cancer vaccines.
Here, a new strategy that TF antigen covalently coupled with KRN7000
and vizantin was developed. The resulting three-component vaccine
KRN7000-TF-vizantin simultaneously triggers invariant natural killer
T (iNKT) cells and macrophage-inducible C-type lectin (Mincle) signaling
pathways, eliciting much stronger TF-specific immune responses than
glycoprotein vaccine TF-KLH/alum and the corresponding two-component
conjugate vaccines TF-KRN7000 and TF-vizantin. The analysis of IgG
isotypes and the secretion of cytokines revealed that KRN7000-TF-vizantin
induced Th1/Th2 mixed immune responses, where Th1 was dominant. In vivo experiments demonstrated that KRN7000-TF-vizantin
increased the survival rate and survival time of tumor-challenged
mice, and surviving mice rejected further tumor attacks without any
additional treatment. This work demonstrates that covalently coupled
KRN7000 and vizantin could serve as a promising TF-based vaccine carrier
for antitumor immune therapy, and KRN7000-TF-vizantin features great
potential to be a vaccine candidate.