Fully Synthetic\nTF-Based Self-Adjuvanting Vaccine\nSimultaneously Triggers iNKT Cells and Mincle and Protects Mice against\nTumor Development

The Thomsen–Friedenreich (TF) antigen has proven\nto be a\npromising target for developing novel therapeutic cancer vaccines.\nHere, a new strategy that TF antigen covalently coupled with KRN7000\nand vizantin was developed. The resulting three-component vaccine\nKRN7000-TF-vizantin simultaneously triggers invariant natural killer\nT (iNKT) cells and macrophage-inducible C-type lectin (Mincle) signaling\npathways, eliciting much stronger TF-specific immune responses than\nglycoprotein vaccine TF-KLH/alum and the corresponding two-component\nconjugate vaccines TF-KRN7000 and TF-vizantin. The analysis of IgG\nisotypes and the secretion of cytokines revealed that KRN7000-TF-vizantin\ninduced Th1/Th2 mixed immune responses, where Th1 was dominant. <i>In vivo</i> experiments demonstrated that KRN7000-TF-vizantin\nincreased the survival rate and survival time of tumor-challenged\nmice, and surviving mice rejected further tumor attacks without any\nadditional treatment. This work demonstrates that covalently coupled\nKRN7000 and vizantin could serve as a promising TF-based vaccine carrier\nfor antitumor immune therapy, and KRN7000-TF-vizantin features great\npotential to be a vaccine candidate.