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癌症免疫治疗的类疫苗纳米医学。

Vaccine-like nanomedicine for cancer immunotherapy.

机构信息

Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.

School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.

出版信息

J Control Release. 2023 Mar;355:760-778. doi: 10.1016/j.jconrel.2023.02.015. Epub 2023 Feb 24.


DOI:10.1016/j.jconrel.2023.02.015
PMID:36822241
Abstract

The successful clinical application of immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapeutics has attracted extensive attention to immunotherapy, however, their drawbacks such as limited specificity, persistence and toxicity haven't met the high expectations on efficient cancer treatments. Therapeutic cancer vaccines which instruct the immune system to capture tumor specific antigens, generate long-term immune memory and specifically eliminate cancer cells gradually become the most promising strategies to eradicate tumor. However, the disadvantages of some existing vaccines such as weak immunogenicity and in vivo instability have restricted their development. Nanotechnology has been recently incorporated into vaccine fabrication and exhibited promising results for cancer immunotherapy. Nanoparticles promote the stability of vaccines, as well as enhance antigen recognition and presentation owing to their nanometer size which promotes internalization of antigens by phagocytic cells. The surface modification with targeting units further permits the delivery of vaccines to specific cells. Meanwhile, nanocarriers with adjuvant effect can improve the efficacy of vaccines. In addition to classic vaccines composed of antigens and adjuvants, the nanoparticle-mediated chemotherapy, radiotherapy and certain other therapeutics could induce the release of tumor antigens in situ, which therefore effectively simulate antitumor immune responses. Such vaccine-like nanomedicine not only kills primary tumors, but also prevents tumor recurrence and helps eliminate metastatic tumors. Herein, we introduce recent developments in nanoparticle-based delivery systems for antigen delivery and in situ antitumor vaccination. We will also discuss the remaining opportunities and challenges of nanovaccine in clinical translation towards cancer treatment.

摘要

免疫检查点阻断 (ICB) 和嵌合抗原受体 T 细胞 (CAR-T) 疗法的成功临床应用引起了人们对免疫疗法的广泛关注,然而,它们的局限性,如有限的特异性、持久性和毒性,并没有达到高效治疗癌症的高期望。治疗性癌症疫苗可以指导免疫系统捕获肿瘤特异性抗原,产生长期免疫记忆,并特异性地消除癌细胞,逐渐成为根除肿瘤的最有前途的策略。然而,一些现有疫苗的缺点,如弱免疫原性和体内不稳定性,限制了它们的发展。纳米技术最近被纳入疫苗的制造中,并在癌症免疫治疗中显示出有前途的结果。由于纳米颗粒的纳米尺寸促进了吞噬细胞对内源性抗原的内化,因此纳米颗粒促进了疫苗的稳定性,同时增强了抗原的识别和呈递。通过靶向单元的表面修饰进一步允许将疫苗递送到特定的细胞。同时,具有佐剂作用的纳米载体可以提高疫苗的疗效。除了由抗原和佐剂组成的经典疫苗外,纳米颗粒介导的化疗、放疗和某些其他治疗方法可以原位诱导肿瘤抗原的释放,从而有效地模拟抗肿瘤免疫反应。这种类似疫苗的纳米医学不仅可以杀死原发性肿瘤,还可以防止肿瘤复发,并有助于消除转移性肿瘤。在此,我们介绍了基于纳米颗粒的抗原传递和原位抗肿瘤疫苗接种的递药系统的最新进展。我们还将讨论纳米疫苗在癌症治疗的临床转化中仍然存在的机会和挑战。

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[5]
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[6]
Cancer Nanovaccines: Mechanisms, Design Principles, and Clinical Translation.

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[7]
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[8]
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[9]
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[10]
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