Department of Radiology, Division Translational Nanobiomaterials and Imaging, Leiden University Medical Center, Leiden, The Netherlands; JeNaCell GmbH, Winzerlaer Straße 2, 07745 Jena, Germany.
Department of Radiology, Division Translational Nanobiomaterials and Imaging, Leiden University Medical Center, Leiden, The Netherlands.
J Control Release. 2018 Sep 10;285:56-66. doi: 10.1016/j.jconrel.2018.07.011. Epub 2018 Jul 6.
Cancer immunotherapy is emerging as a candidate treatment modality for treating post-surgical metastasis and recurrences. Despite the great promises with therapeutic cancer vaccines and checkpoint blocking antibodies in pre-clinical studies, response rates in the clinic still remain unsatisfactory. The evaluation of immunotherapy after surgery in patients could confront significant unexpected hurdles. Surgery itself tends to cause immune suppression, while wound healing factors also stimulate tumor cell outgrowth and metastasis. Regarding the marked changes in the post-surgical tumor microenvironment, one can anticipate that better tumor growth control is attainable by combining cancer vaccines with immune checkpoint blockade. However, it is important that vaccines and checkpoint blocking antibodies are delivered efficiently to their target cells, are released sustained and locally and do not induce cytotoxic effects. The generation of effective anti-tumor immunity and durable response rates could largely depend on these parameters. In the last decade, researchers spend tremendous effort in optimizing the delivery of immunotherapeutic compounds with the use of nanomedicine. Biocompatible nanoparticle based delivery systems demonstrated intriguing results with regard to specific immune cell activation, improved drug delivery, cell targeting, limiting off target toxicity and improving treatment outcome. It therefore makes sense, to speculate on the promises of combined cancer vaccination and immune checkpoint blocking immunotherapy with the aid of nanomedicine. A powerful nanoparticle combination immunotherapy conferring durable therapeutic benefit whilst leaving healthy tissue untouched represents the base for more efficient post-surgical cancer treatment.
癌症免疫疗法作为一种治疗术后转移和复发的候选治疗方法正在出现。尽管在临床前研究中,治疗性癌症疫苗和检查点阻断抗体有很大的前景,但临床反应率仍然不尽如人意。在手术后评估免疫疗法在患者中的应用可能会面临重大的意外障碍。手术本身往往会导致免疫抑制,而伤口愈合因素也会刺激肿瘤细胞的生长和转移。鉴于手术后肿瘤微环境的明显变化,可以预期通过将癌症疫苗与免疫检查点阻断联合使用,可以更好地控制肿瘤生长。然而,重要的是,疫苗和检查点阻断抗体能够有效地递送到靶细胞,持续且局部地释放,并且不会引起细胞毒性作用。有效的抗肿瘤免疫和持久的反应率在很大程度上取决于这些参数。在过去的十年中,研究人员投入了大量精力,通过使用纳米医学来优化免疫治疗化合物的传递。基于生物相容性纳米粒子的递药系统在特定免疫细胞激活、改善药物递送、细胞靶向、限制脱靶毒性和改善治疗效果方面显示出了有趣的结果。因此,借助纳米医学来推测联合癌症疫苗接种和免疫检查点阻断免疫疗法的前景是有意义的。一种强大的纳米粒子联合免疫疗法可以提供持久的治疗益处,同时不影响健康组织,这是更有效的术后癌症治疗的基础。