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试验观察:基于肽的疫苗在抗癌治疗中的应用

Trial watch: Peptide-based vaccines in anticancer therapy.

作者信息

Bezu Lucillia, Kepp Oliver, Cerrato Giulia, Pol Jonathan, Fucikova Jitka, Spisek Radek, Zitvogel Laurence, Kroemer Guido, Galluzzi Lorenzo

机构信息

Faculty of Medicine, University of Paris Sud/Paris XI, Le Kremlin-Bicêtre, France.

Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.

出版信息

Oncoimmunology. 2018 Sep 6;7(12):e1511506. doi: 10.1080/2162402X.2018.1511506. eCollection 2018.

Abstract

Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics. CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen.

摘要

基于肽的抗癌疫苗接种旨在通过用纯化的、重组的或合成工程化表位进行免疫接种来刺激针对一种或多种肿瘤相关抗原(TAA)的免疫反应。尽管寄予厚望,但迄今为止在临床上探索的基于肽的疫苗治疗活性有限,这主要是由于癌细胞内在改变使抗原性降至最低和/或肿瘤微环境变化促进免疫抑制。已经开发了几种策略来克服这些限制,包括使用免疫刺激佐剂、与能够协同释放损伤相关分子模式的细胞毒性抗癌疗法联合治疗以及同时阻断免疫检查点。基于个性化肽的疫苗也正在临床中探索其治疗活性。在此,我们综述了基于肽的疫苗作为抗癌治疗药物使用的近期临床前和临床进展。CMP:碳水化合物模拟肽;CMV:巨细胞病毒;DC:树突状细胞;FDA:美国食品药品监督管理局;HPV:人乳头瘤病毒;MDS:骨髓增生异常综合征;MHP:黑色素瘤辅助疫苗;NSCLC:非小细胞肺癌;ODD:孤儿药指定;PPV:个性化肽疫苗接种;SLP:合成长肽;TAA:肿瘤相关抗原;TNA:肿瘤新抗原。

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