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端粒酶靶向癌症免疫治疗的临床研究进展:文献综述

Clinical research progress of telomerase targeted cancer immunotherapy: a literature review.

作者信息

Wang Yu, Zhang Xiaoying, Chen Guangming, Shao Mingzhe

机构信息

Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou University, Huzhou, China.

Department of Vascular Surgery, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

出版信息

Transl Cancer Res. 2024 Jul 31;13(7):3904-3921. doi: 10.21037/tcr-24-196. Epub 2024 Jul 17.

Abstract

BACKGROUND AND OBJECTIVE

Telomerase is activated or overexpressed in 85-90% of tumors, which maintains the length of telomere and has become an important anti-cancer target. Increasing clinical and preclinical data suggest that telomerase-targeted cancer immunotherapy could achieve effective killing of tumor cells . This article reviews the research progress of telomerase targeted cancer immunotherapy in clinical and pre-clinical trials, aiming to provide a reference for further clinical research and treatment of cancers.

METHODS

We investigated the research progress of telomerase immunotherapy in the last 20 years from four electronic databases.

KEY CONTENT AND FINDINGS

Telomerase-targeted immunotherapies have been developed with the arising of a new era in immuno-oncology, including peptide vaccines, DNA vaccines, dendritic cells (DCs), adoptive cell transfer (ACT) therapies, antibodies, etc. Some of them have been approved for undergoing clinical trials by the Food and Drug Administration (FDA) for the treatment of various cancers, such as pancreatic cancer, non-small cell lung cancer, melanoma, leukaemia. Of all the treatment modalities, vaccines are the primary treatment methods, some of which have been even entered into phase III clinical trials. The main clinical application direction of telomerase vaccine is the combination with other drugs and treatment modalities, including combination with other vaccines targeting human telomerase reverse transcriptase (hTERT), traditional chemotherapy drugs and immunosuppressors. We also summarized the recent findings of immunotherapy targeting hTERT, focusing on various vaccines and the current status of associated clinical trials. We further discussed the advantages, disadvantages and potential developmental directions of various telomerase-targeted immunotherapies.

CONCLUSIONS

Telomerase-targeted cancer immunotherapy has promising prospects in improving patient survival expectancy. This review may provide data support and design ideas for all researchers and pharmaceutical enterprises in this field.

摘要

背景与目的

端粒酶在85%-90%的肿瘤中被激活或过度表达,其维持端粒长度,已成为重要的抗癌靶点。越来越多的临床和临床前数据表明,靶向端粒酶的癌症免疫疗法可有效杀伤肿瘤细胞。本文综述了靶向端粒酶的癌症免疫疗法在临床和临床前试验中的研究进展,旨在为癌症的进一步临床研究和治疗提供参考。

方法

我们从四个电子数据库调查了过去20年中端粒酶免疫疗法的研究进展。

关键内容与发现

随着免疫肿瘤学新时代的到来,已开发出多种靶向端粒酶的免疫疗法,包括肽疫苗、DNA疫苗、树突状细胞(DC)、过继性细胞转移(ACT)疗法、抗体等。其中一些已获美国食品药品监督管理局(FDA)批准进行临床试验,用于治疗各种癌症,如胰腺癌、非小细胞肺癌、黑色素瘤、白血病。在所有治疗方式中,疫苗是主要治疗方法,其中一些甚至已进入III期临床试验。端粒酶疫苗的主要临床应用方向是与其他药物及治疗方式联合,包括与其他靶向人端粒酶逆转录酶(hTERT)的疫苗、传统化疗药物和免疫抑制剂联合。我们还总结了靶向hTERT免疫疗法的最新研究结果,重点关注各种疫苗及相关临床试验现状。我们进一步讨论了各种靶向端粒酶免疫疗法的优缺点及潜在发展方向。

结论

靶向端粒酶的癌症免疫疗法在提高患者生存预期方面前景广阔。本综述可为该领域的所有研究人员和制药企业提供数据支持和设计思路。

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