Department of Radiation Oncology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Laboratory of Nano- and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, Lineberger Comprehensive Cancer Center, Department of Radiation Oncology, University of North Carolina at Chapel Hill, USA.
Adv Drug Deliv Rev. 2019 Apr;144:3-15. doi: 10.1016/j.addr.2019.07.009. Epub 2019 Jul 19.
Cancer immunotherapy is one of the fastest growing and most promising fields in clinical oncology. T-cell checkpoint inhibitors are revolutionizing the management of advanced cancers including non-small cell lung cancer and melanoma. Unfortunately, many common cancers are not responsive to these drugs and resistance remains problematic. A growing number of novel cancer immunotherapies have been discovered but their clinical translation has been limited by shortcomings of conventional drug delivery. Immune signaling is tightly-regulated and often requires simultaneous or near-simultaneous activation of multiple signals in specific subpopulations of immune cells. Nucleic acid therapies, which require intact intracellular delivery, are among the most promising approaches to modulate the tumor microenvironment to a pro-immunogenic phenotype. Advanced nanomedicines can be precisely engineered to overcome many of these limitations and appear well-poised to enable the clinical translation of promising cancer immunotherapies.
癌症免疫疗法是临床肿瘤学中发展最快、最有前途的领域之一。T 细胞检查点抑制剂正在彻底改变晚期癌症的治疗,包括非小细胞肺癌和黑色素瘤。不幸的是,许多常见的癌症对这些药物没有反应,而且耐药性仍然是一个问题。越来越多的新型癌症免疫疗法已经被发现,但由于传统药物输送的缺陷,它们的临床转化受到限制。免疫信号受到严格调节,通常需要在免疫细胞的特定亚群中同时或近乎同时激活多个信号。需要完整的细胞内递送来发挥作用的核酸疗法是调节肿瘤微环境向免疫原性表型的最有前途的方法之一。先进的纳米药物可以被精确地设计,以克服许多这些限制,并有望使有前途的癌症免疫疗法的临床转化成为可能。