接种疫苗
药理学
免疫原性
内科学
兴奋剂
胰腺癌
肺癌
TLR7型
免疫学
作者
Jiae Koh,Sohyun Kim,Sang Nam Lee,Sun-Young Kim,Jung-Eun Kim,Kyoung Young Lee,Mi Soon Kim,Jae Yeong Heo,Young Mee Park,Bo Mi Ku,Jong-Mu Sun,Se-Hoon Lee,Jin Seok Ahn,Keunchil Park,Siyoung Yang,Sang-Jun Ha,Yong Taik Lim,Myung-Ju Ahn
标识
DOI:10.1016/j.nano.2021.102415
摘要
Although immune checkpoint inhibitors have significantly improved clinical outcomes in various malignant cancers, only a small proportion of patients reap benefits, likely due to the low number of T cells and high number of immunosuppressive cells in the tumor microenvironment (TME) of patients with advanced disease. We developed a cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) and analyzed its therapeutic effect alone or in combination with immune checkpoint inhibitors, on antitumor immune responses and the reprogramming of suppressive immune cells in the TME. NE (R848) demonstrated robust local and systemic antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, inducing tumor-specific T cell activation and mitigating T cell exhaustion. Combination with anti-PD-1 antibodies showed synergistic effects with respect to therapeutic efficacy and survival rate. Thus, NE (R848)-based cancer vaccines could prevent tumor recurrence and prolong survival by activating antitumor immunity and reprogramming immunosuppression.
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