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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Immune Checkpoint Inhibitors: An Introduction to the Next-Generation Cancer Immunotherapy
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Immune Checkpoint Inhibitors: An Introduction to the Next-Generation Cancer Immunotherapy

机译：免疫检查点抑制剂：下一代癌症免疫疗法简介

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摘要

Activating the immune system to eliminate cancer cells and produce clinically relevant responses has been a long-standing goal of cancer research. Most promising therapeutic approaches to activating antitumor immunity include immune checkpoint inhibitors. Immune checkpoints are numerous inhibitory pathways hardwired in the immune system. They are critical for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors regulate certain immune checkpoint pathways as a major mechanism of immune resistance. Because immune checkpoints are initiated by ligand-receptor interactions, blockade by antibodies provides a rational therapeutic approach. Although targeted therapies are clinically successful, they are often short-lived due to rapid development of resistance. Immunotherapies offer one notable advantage. Enhancing the cell-mediated immune response against tumor cells leads to generation of a long-term memory lymphocyte population patrolling the body to attack growth of any new tumor cells, thereby sustaining the therapeutic effects. Furthermore, early clinical results suggest that combination immunotherapies offer even more potent antitumor activity. This review is intended to provide an introduction to immune checkpoint inhibitors and discusses the scientific overview of cancer immunotherapy, mechanisms of the inhibitors, clinical pharmacology considerations, advances in combination therapies, and challenges in drug development.
机译：激活免疫系统消除癌细胞并产生临床相关反应一直是癌症研究的长期目标。激活抗肿瘤免疫力的最有希望的治疗方法包括免疫检查点抑制剂。免疫检查点是免疫系统中许多固定的抑制途径。它们对于维持自我耐受以及调节外周组织中生理免疫反应的持续时间和幅度，以最大程度地减少附带组织损害至关重要。肿瘤调节某些免疫检查点途径是免疫抵抗的主要机制。因为免疫检查点是由配体-受体相互作用引发的，所以抗体的阻断提供了一种合理的治疗方法。尽管靶向疗法在临床上是成功的，但由于耐药性的迅速发展，它们通常寿命很短。免疫疗法提供了一个显着的优势。增强针对肿瘤细胞的细胞介导的免疫反应会导致长期记忆的淋巴细胞群的产生，该种群在身体上巡逻以攻击任何新的肿瘤细胞的生长，从而维持治疗效果。此外，早期的临床结果表明联合免疫疗法可提供更强的抗肿瘤活性。这篇综述旨在提供免疫检查点抑制剂的介绍，并讨论癌症免疫疗法的科学概述，抑制剂的机理，临床药理学考虑，联合疗法的进展以及药物开发中的挑战。

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