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细胞因子:改善免疫疗法的信号?

Cytokines: Signalling Improved Immunotherapy?

机构信息

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Tasmania, Australia.

出版信息

Curr Oncol Rep. 2021 Jul 16;23(9):103. doi: 10.1007/s11912-021-01095-x.

Abstract

PURPOSE OF REVIEW

Immune checkpoint immunotherapies (ICI) are now approved for over 20 types of cancer and there are almost 6000 ongoing clinical trials investigating immuno-modulators as cancer therapies. This review investigated the effect of monoclonal antibody-based immune checkpoint immunotherapies when combined with cytokine therapy. We reviewed published clinical trial results from 2005 to 2020 for studies that used approved monoclonal antibody ICI in combination with the cytokines. Studies that met the search criteria were assessed for treatment efficacy and immunological changes associated with treatment.

RECENT FINDING

ICI often fails to result in improved clinical outcomes for patients and lasting protection from cancer recurrence. The use of pro-inflammatory cytokines alongside ICI has been shown to enhance the efficacy of these therapies in vitro and in animal studies. However, the results in human clinical trials are less clear and many clinical trials do not publish results at the end of the trial. A deeper understanding of the molecular interactions between cytokines, tumors, and immune cells is needed to improve overall ICI outcomes and design combination trials. Critical examination of the design and characteristics of previous clinical trials can provide insight into the lack of effective clinical translation for many immunotherapeutic drugs.

摘要

目的综述

免疫检查点免疫疗法(ICI)目前已获批用于 20 多种癌症,目前有近 6000 项临床试验正在研究免疫调节剂作为癌症疗法。本综述调查了单克隆抗体为基础的免疫检查点免疫疗法与细胞因子疗法联合应用的效果。我们回顾了 2005 年至 2020 年期间发表的临床研究结果,这些研究使用了已批准的单克隆抗体 ICI 联合细胞因子。对符合检索标准的研究进行了治疗效果评估,并评估了与治疗相关的免疫学变化。

最新发现

ICI 通常未能改善患者的临床预后,也不能持久预防癌症复发。在体外和动物研究中,与 ICI 联合使用促炎细胞因子已被证明可提高这些疗法的疗效。然而,在人体临床试验中的结果并不明确,许多临床试验在试验结束时并未公布结果。需要更深入地了解细胞因子、肿瘤和免疫细胞之间的分子相互作用,以提高整体 ICI 疗效并设计联合试验。对以前临床试验的设计和特点进行批判性分析,可以深入了解许多免疫治疗药物在临床转化方面缺乏有效性的原因。

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