Murad Yanal M, Clay Timothy M, Lyerly H Kim, Morse Michael A
Duke University Medical Center, Department of Surgery, Program in Molecular Therapeutics, Comprehensive Cancer Center, Durham, NC 27710, USA.
Expert Opin Biol Ther. 2007 Aug;7(8):1257-66. doi: 10.1517/14712598.7.8.1257.
Stimulation of toll-like receptor (TLR)9 activates human plasmacytoid dendritic cells and B cells, and induces potent innate immune responses in preclinical tumor models and in patients. CpG oligodeoxynucleotides (ODNs) are TLR9 agonists that show promising results as vaccine adjuvants and in the treatment of cancers, infections, asthma and allergy. PF-3512676 (ProMune) was developed as a TLR9 agonist for the treatment of cancer as monotherapy and as an adjuvant in combination with chemo- and immunotherapy. Phase I and II trials have tested this drug in several hematopoietic and solid tumors. Pfizer has initiated Phase III trials to test PF-3512676 in combination with standard chemotherapy for non-small-cell lung cancer.
Toll样受体（TLR）9的刺激可激活人浆细胞样树突状细胞和B细胞，并在临床前肿瘤模型和患者中诱导强大的先天免疫反应。CpG寡脱氧核苷酸（ODN）是TLR9激动剂，作为疫苗佐剂以及在癌症、感染、哮喘和过敏治疗中显示出有前景的结果。PF-3512676（ProMune）被开发为一种TLR9激动剂，用于癌症的单药治疗以及与化疗和免疫疗法联合作为佐剂。I期和II期试验已在多种血液系统肿瘤和实体瘤中对该药物进行了测试。辉瑞已启动III期试验，以测试PF-3512676与标准化疗联合用于非小细胞肺癌的疗效。
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