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[针对胶质瘤的免疫疗法]

[Immunotherapy against gliomas].

作者信息

Sahm Katharina, Weiss Tobias

机构信息

Neurologische Klinik, Medizinische Fakultät Mannheim, MCTN, Universität Heidelberg, Mannheim, Deutschland.

Klinische Kooperationseinheit Neuroimmunologie und Hirntumorimmunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Deutschland.

出版信息

Nervenarzt. 2024 Feb;95(2):111-116. doi: 10.1007/s00115-023-01590-5. Epub 2024 Jan 2.

Abstract

BACKGROUND

Gliomas represent the most frequent malignant primary brain tumors in adults. Despite multimodal treatment concepts involving surgery, irradiation and chemotherapy, the prognosis remains poor and they are incurable. Recent insights into the interactions between the immune system and the central nervous system as well as breakthroughs in the results of other cancer types have led to the fact that various immunotherapeutic approaches against gliomas have also been investigated and in some cases specifically developed.

OBJECTIVE

This article provides an overview of the current status of different immunotherapeutic concepts against gliomas, highlighting the advantages, disadvantages, and challenges. Additionally, it provides an overview of currently ongoing immunotherapeutic clinical trials in Germany and neighboring countries.

RESULTS

Previous randomized studies on antibodies against programmed cell death protein 1 (anti-PD1) immune checkpoint inhibition, viral treatment and peptide vaccination targeting the variant III of the epidermal growth factor receptor (EGFRvIII) in glioblastomas were negative with respect to survival benefits. Conversely, other immunotherapeutic approaches, such as multivalent or driver mutation-based vaccinations, cytokine-based therapy and cell therapy, demonstrated a robust scientific foundation, with at least early studies showing promising safety and pharmacodynamic effects on the tumors.

DISCUSSION

Currently, immunotherapies against gliomas should only be applied within the framework of well-designed clinical studies. There are still many knowledge gaps regarding the mechanisms of action and resistance of various immunotherapies. Accompanying translational research is essential to address these gaps and develop more effective therapies.

摘要

背景

胶质瘤是成人中最常见的原发性恶性脑肿瘤。尽管采用了包括手术、放疗和化疗在内的多模式治疗方案,但预后仍然很差,无法治愈。最近对免疫系统与中枢神经系统之间相互作用的深入了解以及其他癌症类型治疗结果的突破,使得针对胶质瘤的各种免疫治疗方法也得到了研究,并且在某些情况下是专门开发的。

目的

本文概述了针对胶质瘤的不同免疫治疗概念的现状,强调了其优点、缺点和挑战。此外,还概述了德国及周边国家目前正在进行的免疫治疗临床试验。

结果

先前关于抗程序性细胞死亡蛋白1(抗PD1)免疫检查点抑制、病毒治疗和针对胶质母细胞瘤表皮生长因子受体变体III(EGFRvIII)的肽疫苗接种的随机研究在生存获益方面均为阴性。相反,其他免疫治疗方法,如多价或基于驱动基因突变的疫苗接种、基于细胞因子的治疗和细胞治疗,显示出坚实的科学基础,至少早期研究表明对肿瘤具有良好 的安全性和药效学作用。

讨论

目前,针对胶质瘤的免疫疗法应仅在精心设计的临床研究框架内应用。关于各种免疫疗法的作用机制和耐药性仍存在许多知识空白。开展配套的转化研究对于填补这些空白和开发更有效的疗法至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61ce/10850214/b22043255ffe/115_2023_1590_Fig1_HTML.jpg

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