Genetically-engineered"all-in-one"vaccine platform for cancer immunotherapy

• 作者: Aihua Wu Yingzhi Chen Hairui Wang Ya Chang Meng Zhang Pengfei Zhao Yisi Tang Qin Xu Zhuangzhi Zhu Yang Cao Yongzhuo Huang
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Origimal articles
• 页码范围: 3622-3635
• 页数: 14页
• 语种: 英文

摘要

An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity.A major hurdle against cancer therapeutic vaccination is the insufficient im-mune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use.We discovered a novel cancer immunostimulant,trichosanthin(TCS),that is a clinically used protein drug in China,and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide,TCS,and a cell-penetrating peptide(CPP),termed an"all-in-one"vaccine,for transcutaneous cancer immunization.The TCS adjuvant effect on antigen presenta-tion was investigated and the antitumor immunity of the vaccines was investigated using the different tu-mor models.The vaccines were prepared via a facile recombinant method.The vaccines induced the maturation of DCs that subsequently primed CD8+T cells.The TCS-based immunostimulation was asso-ciated with the STING pathway.The general applicability of this genetic engineering strategy was demonstrated with various tumor antigens(i.e.,legumain and TRP2 antigenic peptides)and tumor models(i.e.,colon tumor and melanoma).These findings represent a useful protocol for developing cancer vac-cines at low cost and time-saving,and demonstrates the adjuvant application of TCS—an old drug for a new application.