Nakamura Takashi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University.
Yakugaku Zasshi. 2018;138(12):1443-1449. doi: 10.1248/yakushi.18-00162.
The appearance of immune checkpoint inhibitors has been a major turning point in cancer therapy. The success of immune checkpoint therapy has revolutionized the field of cancer therapy, and immunotherapy has joined the cancer treatment ranks as a pillar. To induce effective anti-tumor immune responses, it is necessary both to enhance the activity of immune cells and to block immune suppression by tumor cells. Carrier type drug delivery systems based on nanobiotechnology (nano DDS) represent a potentially useful technology for efficiently achieving both: enhancement of the activity of immune cells and blocking immune suppression. It has become clear that nano DDS can improve the practical utility of a wide variety of immune functional molecules and thus regulate drug kinetics and intracellular dynamics to improve drug efficacy and reduce side effects. We have been in the process of developing a nano DDS for the enhancement of cancer immunotherapy. A nano DDS encapsulating an agonist of a simulated interferon gene pathway greatly enhanced the activity of the agent's antitumor immune response. To block immune suppression, we successfully developed a small interfering RNA loaded into a nano DDS which regulates gene expression in immune cells. In this review, we summarize our recent efforts regarding cancer immunotherapy using nano DDS.
免疫检查点抑制剂的出现是癌症治疗的一个重大转折点。免疫检查点疗法的成功彻底改变了癌症治疗领域,免疫疗法已成为癌症治疗的一大支柱。为了诱导有效的抗肿瘤免疫反应,既需要增强免疫细胞的活性,又要阻断肿瘤细胞的免疫抑制作用。基于纳米生物技术的载体型药物递送系统(纳米药物递送系统)是一种可能有效实现这两点的技术:增强免疫细胞活性和阻断免疫抑制。很明显,纳米药物递送系统可以提高各种免疫功能分子的实际效用,从而调节药物动力学和细胞内动态变化,以提高药物疗效并减少副作用。我们一直在开发用于增强癌症免疫治疗的纳米药物递送系统。一种包裹模拟干扰素基因途径激动剂的纳米药物递送系统极大地增强了该药物的抗肿瘤免疫反应活性。为了阻断免疫抑制,我们成功开发了一种装载在纳米药物递送系统中的小干扰RNA,它可调节免疫细胞中的基因表达。在这篇综述中,我们总结了我们最近在使用纳米药物递送系统进行癌症免疫治疗方面所做的努力。