Potentiation of cancer immunotherapy using spatiotemporal regulation of heat shock protein-TLR ligand complex

我们已经证明，Hsp90可以通过时空调节作为相关抗原肽的有效诱导剂。我们研究了Hsp90抗原肽复合体和TLR配体免疫是否通过交叉压力增强了细胞毒性T细胞(CTL)反应的诱导。有趣的是，血浆细胞样树突状细胞(PDC)在给予CpG-A后不仅能分泌干扰素-α，还能分泌HSP72。我们发现，分泌的HSP72与Hsp90-多肽形成了复合体，导致了对相关多肽的高效交叉压力和CTL诱导。这些数据表明，CpG-A是基于Hsp90的癌症疫苗的良好候选免疫佐剂。

We have demonstrated that Hsp90 can act as an efficient inducer for crosspresentation of associated antigenic peptide via spatiotemporal regulation. We examined whether vaccination with Hsp90-antigen peptide complex and TLR ligand augmented the induction of cytotoxic T cell (CTL) response via crosspresentation. Interestingly, plasmacytoid dendritic cells (pDCs) secreted not only IFN-a but also Hsp72 in response to CpG-A administration. We found that the secreted Hsp72 formed complex with Hsp90-peptide complex, leading to the efficient crosspresentation and CTL induction against associated peptide. These data suggest that CpG-A is a good candidate as an immunoadjuvant for Hsp90-based cancer vaccine.