抗原
癌症免疫疗法
交叉展示
免疫系统
CTL公司*
化学
免疫疗法
癌症疫苗
细胞毒性T细胞
癌症研究
卵清蛋白
癌症
免疫学
佐剂
抗原呈递
癌细胞
T细胞
医学
CD8型
内科学
生物化学
体外
作者
Hanfei Wu,Qi Zhuang,Jun Xu,Ligeng Xu,Yuhuan Zhao,Chao Wang,Zongjin Yang,Fengyun Shen,Zhuang Liu,Rui Peng
标识
DOI:10.1021/acs.bioconjchem.9b00245
摘要
The development of effective cancer vaccines is an important direction in the area of cancer immunotherapy. Although certain types of preventive cancer vaccines have already been used in the clinic, therapeutic cancer vaccines for treatment of already established tumors are still in high demand. In this study, we develop a new type of cancer vaccine by mixing cell-penetrating peptide (CPP) conjugated antigen as the enhanced antigen, together with CpG as the immune adjuvant. A special CPP, cytosol-localizing internalization peptide 6 (CLIP6), which has the ability to enter cells exclusively via a nonendosomal mechanism, i.e., direct translocation across the cell membrane, is conjugated with model antigen ovalbumin (OVA). Compared to naked OVA, the obtained CLIP6-OVA conjugates show greatly increased uptake by dendritic cells (DCs) and, more importantly, remarkably enhanced antigen cross-presentation, eliciting stronger cytotoxic T lymphocyte (CTL) mediated immune responses with the help of CpG. This CLIP6-OVA/CpG formulation offers effective protection for mice against challenged B16-OVA tumors, and is able to further function as a therapeutic vaccine, which, in combination with immune checkpoint blockade therapy, can significantly suppress the already-established tumors. Such a CLIP6-based cancer vaccine developing strategy shows promising potential toward clinical practice owing to its features of easy preparation, low cost, and remarkable biocompatibility.
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