合成生物学 ›› 2024, Vol. 5 ›› Issue (2): 239-253.DOI: 10.12211/2096-8280.2023-061
方超1, 黄卫人1,2,3
收稿日期:
2023-08-25
修回日期:
2024-02-29
出版日期:
2024-04-30
发布日期:
2024-04-28
通讯作者:
黄卫人
作者简介:
基金资助:
Chao FANG1, Weiren HUANG1,2,3
Received:
2023-08-25
Revised:
2024-02-29
Online:
2024-04-30
Published:
2024-04-28
Contact:
Weiren HUANG
摘要:
根据中心法则和细胞免疫学原则,利用合成生物学设计和生产新型肿瘤疫苗代表了癌症免疫治疗中的一个重要途径。本文概述了利用合成生物学针对两个主要方面(抗原选择和疫苗设计)的创新治疗性肿瘤疫苗的最新研究进展。针对肿瘤相关或特定抗原,开发更精确和有效的肿瘤疫苗引起了广泛关注。传统方法在抗原选择中主要针对肿瘤中的特定基因,而以高通量测序及质谱为基础筛选新抗原的方法明显改善了疫苗的靶向性及免疫原性。在疫苗类别方面,与传统多肽疫苗相比,通过对DNA、mRNA、病毒/细菌、细胞的工程化修饰而成的新型疫苗显著扩大了肿瘤疫苗的范围,从而大幅增强了不同肿瘤疫苗的免疫效果。合成生物学的快速发展将加速对肿瘤疫苗的实验研究进度,最终导致临床治疗效果的持续增强。
中图分类号:
方超, 黄卫人. 合成生物学在肿瘤疫苗设计中的应用进展[J]. 合成生物学, 2024, 5(2): 239-253.
Chao FANG, Weiren HUANG. Progress with the application of synthetic biology in designing of cancer vaccines[J]. Synthetic Biology Journal, 2024, 5(2): 239-253.
肿瘤抗原 | 抗原类型 | 表达位置 | 高丰度表达位置 |
---|---|---|---|
肿瘤相关性抗原 | 高表达蛋白或者多肽 | 肿瘤或正常细胞 | 肿瘤 |
肿瘤种系抗原 | 肿瘤,生殖细胞 | 肿瘤,生殖细胞 | |
肿瘤特异性抗原 | 肿瘤病毒 | 病毒性肿瘤 | 病毒性肿瘤 |
肿瘤新抗原 | 肿瘤 | 肿瘤 |
表1 肿瘤抗原分类
Table 1 Classification of cancer antigens
肿瘤抗原 | 抗原类型 | 表达位置 | 高丰度表达位置 |
---|---|---|---|
肿瘤相关性抗原 | 高表达蛋白或者多肽 | 肿瘤或正常细胞 | 肿瘤 |
肿瘤种系抗原 | 肿瘤,生殖细胞 | 肿瘤,生殖细胞 | |
肿瘤特异性抗原 | 肿瘤病毒 | 病毒性肿瘤 | 病毒性肿瘤 |
肿瘤新抗原 | 肿瘤 | 肿瘤 |
图2 ALK 多肽疫苗抑制肿瘤转移效果[72](中枢神经系统转移肿瘤实验鼠数量的比例)
Fig. 2 Inhibition of tumor metastasis by ALK peptide vaccine characterized by the number of tested mice with metastatic tumors in their central nervous systems[72]
图3 病人对autogene cevumera疫苗的免疫反应[88](接种新疫苗抗原后,在患者体内收集的PBMC中疫苗诱导的IFNγ+ T细胞数量。R0/R1表示手术切除边缘的状态)
Fig. 3 Immune response of the patients to the autogene cevumera vaccine[88](The number of vaccine-induced IFNγ+ T cells in PBMC collected from the patients after vaccination with new vaccine antigens. R0/R1 indicates surgical resection margin status. Adapted with permission from reference.)
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