Milling Lauren, Zhang Yuan, Irvine Darrell J
Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; Dept. of Biological Engineering, MIT, Cambridge, MA, USA.
Dept. of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, RI, USA.
Adv Drug Deliv Rev. 2017 May 15;114:79-101. doi: 10.1016/j.addr.2017.05.011. Epub 2017 May 22.
Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities. Here we review mechanisms of toxicity for clinically-relevant immunotherapeutics, and discuss approaches based in drug delivery technology to enhance the safety and potency of these treatments. These include strategies to merge drug delivery with adoptive cellular therapies, targeting immunotherapies to tumors or select immune cells, and localizing therapeutics intratumorally. Rational design employing lessons learned from the drug delivery and nanomedicine fields has the potential to facilitate immunotherapy reaching its full potential.
癌症免疫疗法如今已成为强大的临床现实，新药获批稳步推进，还有大量额外治疗手段正处于临床和临床前开发阶段。然而，免疫系统的调节可能是一把双刃剑：激活免疫效应器的药物容易引发严重的非特异性全身性炎症和自身免疫副作用。药物递送技术在利用免疫疗法的力量同时避免靶向肿瘤外毒性方面发挥着重要作用。在此，我们综述了临床相关免疫疗法的毒性机制，并讨论基于药物递送技术提高这些治疗安全性和效力的方法。这些方法包括将药物递送与过继性细胞疗法相结合的策略、使免疫疗法靶向肿瘤或特定免疫细胞以及在肿瘤内定位治疗药物。借鉴药物递送和纳米医学领域经验进行的合理设计，有可能推动免疫疗法充分发挥其潜力。
