Holldack Johanna
Telormedix, Via della Posta 10, CH-6934 Bioggio, Switzerland.
Drug Discov Today. 2014 Apr;19(4):379-82. doi: 10.1016/j.drudis.2013.08.020. Epub 2013 Sep 3.
Stimulation of Toll-like receptors (TLRs) to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3, 4, 7, 8 and 9 are all validated targets for cancer and a number of companies are developing agonists and vaccine adjuvants. TLR7 in particular has established proof-of-concept as a target in the topical treatment of bladder and skin cancers. However, the development of systemic treatments targeting TLR7 for most other cancers has proved difficult owing to cardiotoxicity or myelosuppression. Tantalisingly, recent animal data have demonstrated that a new class of modified TLR7 agonists can be administered systemically with a good toxicology profile, opening up this target in therapeutic interventions for systemic cancers.
多年来，刺激Toll样受体（TLRs）以激活先天免疫系统一直是一种合理的治疗策略。TLR3、4、7、8和9都是已被验证的癌症治疗靶点，多家公司正在开发激动剂和疫苗佐剂。特别是TLR7已被确立为膀胱癌和皮肤癌局部治疗的靶点。然而，由于心脏毒性或骨髓抑制，针对大多数其他癌症的TLR7全身治疗的开发已被证明具有难度。令人兴奋的是，最近的动物数据表明，一类新型的修饰TLR7激动剂可以全身给药，且毒理学特征良好，这为全身性癌症的治疗干预开辟了这一靶点。
