通过全身给药的纳米药物原位接种诱导抗肿瘤 T 细胞免疫。
Induction of anti-cancer T cell immunity by in situ vaccination using systemically administered nanomedicines.
机构信息
Fischell Department of Bioengineering, A. James Clark Hall, Room 5110, 8278 Paint Branch Drive, College Park, MD, 20742, USA; Avidea Technologies, Baltimore, MD, 21205, USA.
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06, Prague, Czech Republic.
出版信息
Cancer Lett. 2019 Sep 10;459:192-203. doi: 10.1016/j.canlet.2019.114427. Epub 2019 Jun 8.
Patients with inadequate anti-cancer T cell responses experience limited benefit from immune checkpoint inhibitors and other immunotherapies that require T cells. Therefore, treatments that induce de novo anti-cancer T cell immunity are needed. One strategy - referred to as in situ vaccination - is to deliver chemotherapeutic or immunostimulatory drugs into tumors to promote cancer cell death and provide a stimulatory environment for priming T cells against antigens already present in the tumor. However, achieving sufficient drug concentrations in tumors without causing dose-limiting toxicities remains a major challenge. To address this challenge, nanomedicines based on nano-sized carriers ('nanocarriers') of chemotherapeutics and immunostimulants are being developed to improve drug accumulation in tumors following systemic (intravenous) administration. Herein, we present the rationale for using systemically administrable nanomedicines to induce anti-cancer T cell immunity via in situ vaccination and provide an overview of synthetic nanomedicines currently used clinically. We also describe general strategies for improving nanomedicine design to increase tumor uptake, including use of micelle- and star polymer-based nanocarriers. We conclude with perspectives for how nanomedicine properties, host factors and treatment combinations can be leveraged to maximize efficacy.
患者的抗肿瘤 T 细胞反应不足,从免疫检查点抑制剂和其他需要 T 细胞的免疫疗法中获益有限。因此,需要诱导新的抗肿瘤 T 细胞免疫的治疗方法。一种策略——称为原位疫苗接种——是将化疗药物或免疫刺激药物递送到肿瘤中,以促进癌细胞死亡,并为针对肿瘤中已存在抗原的 T 细胞提供刺激环境。然而,在不引起剂量限制毒性的情况下,在肿瘤中达到足够的药物浓度仍然是一个主要挑战。为了解决这一挑战,正在开发基于化疗药物和免疫刺激剂的纳米载体(“纳米载体”)的纳米药物,以改善系统(静脉内)给药后肿瘤内的药物积累。在此,我们提出了通过原位疫苗接种使用系统给药的纳米药物诱导抗肿瘤 T 细胞免疫的原理,并概述了目前临床上使用的合成纳米药物。我们还描述了用于提高纳米药物设计以增加肿瘤摄取的一般策略,包括使用胶束和星形聚合物纳米载体。最后,我们展望了如何利用纳米药物特性、宿主因素和治疗组合来最大限度地提高疗效。
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