STIMIT, Cambridge, MA, USA.
Nat Rev Cancer. 2019 Oct;19(10):587-602. doi: 10.1038/s41568-019-0186-9. Epub 2019 Sep 6.
The 2018 Nobel Prize in Physiology or Medicine was awarded to pioneers in the field of cancer immunotherapy, as the utility of leveraging a patient's coordinated and adaptive immune system to fight the patient's unique tumour has now been validated robustly in the clinic. Still, the proportion of patients who respond to immunotherapy remains modest (~15% objective response rate across indications), as tumours have multiple means of immune evasion. The immune system is spatiotemporally controlled, so therapies that influence the immune system should be spatiotemporally controlled as well, in order to maximize the therapeutic index. Nanoparticles and biomaterials enable one to program the location, pharmacokinetics and co-delivery of immunomodulatory compounds, eliciting responses that cannot be achieved upon administration of such compounds in solution. The convergence of cancer immunotherapy, nanotechnology, bioengineering and drug delivery is opportune, as each of these fields has matured independently to the point that it can now be used to complement the others substantively and rationally, rather than modestly and empirically. As a result, unmet needs increasingly can be addressed with deductive intention. This Review explores how nanotechnology and related approaches are being applied to augmenting both endogenous leukocytes and adoptively transferred ones by informing specificity, influencing localization and improving function.
2018 年诺贝尔生理学或医学奖授予癌症免疫疗法领域的先驱者,因为利用患者协调和适应性免疫系统来对抗患者独特肿瘤的效用在临床上已经得到了充分验证。然而,对免疫疗法有反应的患者比例仍然不高(各适应症的客观缓解率约为 15%),因为肿瘤有多种免疫逃逸的手段。免疫系统受到时空控制,因此影响免疫系统的疗法也应该受到时空控制,以最大限度地提高治疗指数。纳米粒子和生物材料使人们能够对免疫调节化合物的位置、药代动力学和共递送来进行编程,从而引发无法通过溶液给药实现的反应。癌症免疫疗法、纳米技术、生物工程和药物输送的融合是适时的,因为这些领域都已经独立地发展成熟,现在可以被用来实质性和理性地补充其他领域,而不是适度地和经验性地。因此,未满足的需求越来越可以通过演绎意图来解决。本综述探讨了纳米技术和相关方法如何通过提高内源性白细胞和过继转移的白细胞的特异性、影响定位和改善功能来增强它们。
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