PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advances in dendritic cell vaccination therapy of cancer.
Advances in dendritic cell vaccination therapy of cancer.
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传统上,疫苗在人类历史上有助于根除多种传染病,也挽救了数百万人的生命。这些预防性疫苗通过诱针对减毒活病原体、灭活病原体或抗原亚单位的免疫反应,保护受种者免受病原微生物引起的真实感染。
然而,作为人类健康重要靶点的抗癌疫苗开发一直面临挑战,需要进一步优化。树突状细胞(DCs)是最有效的抗原提呈细胞(APCs),通过诱导 CD8+ T 细胞免疫在肿瘤免疫治疗中发挥重要作用。
因此,人们测试了多种策略,利用 DCs 作为治疗性疫苗,以发挥其抗肿瘤细胞活性。应用全肿瘤细胞或纯化/重组抗原肽是致敏 DCs 的最常见方法,随后将 DCs 回输给患者。尽管在动物试验和癌症患者临床试验中测试的一些 DC 疫苗报告了一些有希望的结果,但此类方法仍然效率低下,需要优化。DC 疫苗接种失败的原因被推测包括免疫抑制性肿瘤微环境(TME)、检查点蛋白过表达、肿瘤相关抗原(TAA)特异性 T 淋巴细胞亲和力欠佳,以及缺乏合适的佐剂。在这篇综述中,我们概述了当前评估 DC 疫苗接种抗癌疗效的实验和试验,并重点关注提高其潜力的策略,包括与免疫检查点抑制剂(ICIs)联合治疗。
Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions of lives in the human history. Those prophylactic vaccines have acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect the recipient against a real infection caused by the pathogenic microorganism. Nevertheless, development of anticancer vaccines as valuable targets in human health has faced challenges and requires further optimizations. Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) that play essential roles in tumor immunotherapies through induction of CD8 + T cell immunity. Accordingly, various strategies have been tested to employ DCs as therapeutic vaccines for exploiting their activity against tumor cells.
Application of whole tumor cells or purified/recombinant antigen peptides are the most common approaches for pulsing DCs, which then are injected back into the patients. Although some hopeful results are reported for a number of DC vaccines tested in animal and clinical trials of cancer patients, such approaches are still inefficient and require optimization.
Failure of DC vaccination is postulated due to immunosuppressive tumor microenvironment (TME), overexpression of checkpoint proteins, suboptimal avidity of tumor-associated antigen (TAA)-specific T lymphocytes, and lack of appropriate adjuvants. In this review, we have an overview of the current experiments and trials evaluated the anticancer efficacy of DC vaccination as well as focusing on strategies to improve their potential including combination therapy with immune checkpoint inhibitors (ICIs).
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