溶瘤病毒
化学
细胞毒性
免疫疗法
肽
癌症免疫疗法
表位
黑色素瘤
抗菌肽
CD8型
癌症研究
细胞毒性T细胞
免疫系统
体内
抗体
免疫学
生物化学
体外
生物
生物技术
作者
Ye Wu,Dong Li,Yixin Jiang,Jinmei Jin,Sanhong Liu,Lili Chen,Hong Zhang,Yifeng Zhou,Hongzhuan Chen,Dale G. Nagle,Xin Luan,Guoqing Zhang
标识
DOI:10.1021/acs.jmedchem.0c02237
摘要
Peptide stapling chemistry represents an attractive strategy to promote the clinical translation of protein epitope mimetics, but its use has not been applied to natural cytotoxic peptides (NCPs) to produce new oncolytic peptides. Based on a wasp venom peptide, a series of stapled anoplin peptides (StAnos) were prepared. The optimized stapled Ano-3/3s were shown to be protease-resistant and exerted superior tumor cell-selective cytotoxicity by rapid membrane disruption. In addition, Ano-3/3s induced tumor ablation in mice through the direct oncolytic effect and subsequent stimulation of immunogenic cell death. This synergistic oncolytic-immunotherapy effect is more remarkable on melanoma than on triple-negative breast cancer in vivo. The efficacies exerted by Ano-3/3s on melanoma were further characterized by CD8+ T cell infiltration, and the addition of anti-CD8 antibodies diminished the long-term antitumor effects. In summary, these results support stapled peptide chemistry as an advantageous method to enhance the NCP potency for oncolytic therapy.
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