中国癌症杂志 ›› 2024, Vol. 34 ›› Issue (5): 509-516.doi: 10.19401/j.cnki.1007-3639.2024.05.008
收稿日期:
2024-03-04
修回日期:
2024-04-03
出版日期:
2024-05-30
发布日期:
2024-06-07
通信作者:
赵凯(ORCID: 0000-0001-6139-1912),博士,教授,台州学院生命科学学院院长
作者简介:
辛美仪(ORCID: 0009-0005-2834-0298),硕士。
基金资助:
XIN Meiyi1(), LIN Yuhong2, ZHAO Kai1,2(
)
Received:
2024-03-04
Revised:
2024-04-03
Published:
2024-05-30
Online:
2024-06-07
Contact:
ZHAO Kai
文章分享
摘要:
由于传统抗肿瘤手段在临床应用中具有特异度低、不良反应大的缺点,新型的抗肿瘤免疫疗法受到关注并逐渐得以应用。肿瘤免疫疗法通过调节机体免疫系统,增强抗肿瘤免疫应答以实现对肿瘤的控制和杀伤。肿瘤免疫疗法包括免疫检查点阻断疗法、过继细胞免疫治疗和肿瘤疫苗。其中,肿瘤疫苗通过递送肿瘤细胞特异性抗原刺激免疫系统产生特异性免疫细胞或抗体从而消除肿瘤细胞以达到治疗肿瘤的目的。近年来,mRNA疫苗相关领域迅速发展,所需的mRNA在合成及制备方面的工艺日趋成熟,为肿瘤mRNA疫苗的研究奠定了良好的基础。因mRNA具有易被降解、无法自主进入细胞等特点,此类疫苗需要合适的递送载体才能成功地被细胞摄取并发挥功效。因此,mRNA疫苗递送系统的发展成为其能否被更好地利用的关键,这也是在肿瘤治疗领域里mRNA疫苗能否被开发利用至临床阶段的重要一环。本文简要介绍肿瘤的免疫治疗方法、肿瘤疫苗种类和肿瘤mRNA疫苗的作用机制及制备方法,介绍用于肿瘤治疗的免疫疗法中mRNA疫苗及其常见的递送系统的研究进展和相关应用,并对进入临床试验阶段的肿瘤mRNA疫苗进行归纳和整理,以期为今后针对肿瘤的mRNA疫苗的研究工作提供帮助。
中图分类号:
辛美仪, 林玉红, 赵凯. 肿瘤mRNA疫苗及其递送载体在抗肿瘤免疫治疗中的研究进展[J]. 中国癌症杂志, 2024, 34(5): 509-516.
XIN Meiyi, LIN Yuhong, ZHAO Kai. Progress in the development of mRNA vaccine and its delivery systems for anti-tumor immunotherapy[J]. China Oncology, 2024, 34(5): 509-516.
表1
进入临床试验的肿瘤mRNA疫苗"
ClinicalTrials.gov identifier | Phase | Disease | Loaded mRNA | Delivery vehicle |
---|---|---|---|---|
NCT01995708[ | Ⅰ | Multiple myeloma | Cancer-testis antigen 7, melanoma antigen-A3, and Wilms tumor gene (WT1) mRNA | Langerhans-type dendritic cells |
NCT01446731 | Ⅱ | Prostatic neoplasms | PSA, PAP, survivin and hTERT mRNA | Dendritic cells |
NCT00890032 | Ⅰ | Recurrent central nervous system neoplasm | TSA mRNA | Dendritic cells |
NCT02808416 | Ⅰ | Brain cancer, neoplasm metastases | TSA mRNA | Dendritic cells |
NCT00961844 | Ⅰ/Ⅱ | Metastatic malignant melanoma | Survivin and hTERT mRNA | Dendritic cells |
NCT00514189 | Ⅰ | Leukemia | Acute myelogenous leukemia lysate plus mRNA | Dendritic Cells |
NCT01456104 | Ⅰ | Melanoma | TSA mRNA | Langerhans-type dendritic cells |
NCT00834002 | Ⅰ | Acute myeloid leukemia | WT1 mRNA | Dendritic cells |
NCT00639639 | Ⅰ | Prostatic neoplasms | Cytomegalovirus (CMV) pp65-lysosomal-associated membrane protein (LAMP) mRNA | Dendritic cells |
NCT01197625 | Ⅰ/Ⅱ | Prostate cancer | TSA, hTERT and survivin mRNA | Dendritic cells |
NCT01334047 | Ⅰ/Ⅱ | Recurrent epithelial ovarian cancer | TSA, hTERT and survivin. mRNA | Dendritic cells |
NCT00626483 | Ⅰ | Malignant neoplasms brain | CMV pp65-LAMP mRNA | Dendritic cells |
NCT00846456 | Ⅰ/Ⅱ | Glioblastoma, brain tumor | TSA mRNA | Dendritic cells |
NCT02366728 | Ⅱ | Glioblastoma, astrocytoma, grade Ⅳ, giant cell glioblastoma | CMV pp65-LAMP mRNA | Dendritic cells |
NCT04163094 | Ⅰ | Ovarian cancer | TSA mRNA | Liposome |
NCT03927222 | Ⅱ | Glioblastoma | CMV pp65-LAMP mRNA | Dendritic cells |
NCT02465268 | Ⅱ | Glioblastoma multiforme, glioblastoma, malignant glioma | pp65-shLAMP | Dendritic cells |
NCT00228189[ | Ⅰ/Ⅱ | Colorectal cancer, liver metastases | CEA mRNA | Dendritic cells |
NCT03688178 | Ⅱ | Glioblastoma | CMV pp65-LAMP mRNA | Dendritic cells |
NCT00978913 | Ⅰ | Breast cancer, malignant melanoma | Survivin, hTERT and p53 mRNA | Dendritic cells |
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