Is AAV-delivered IL-27 a potential immunotherapeutic for cancer?
Is AAV-delivered IL-27 a potential immunotherapeutic for cancer?
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DOI：
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发表时间：
2020-11
影响因子：
5.3
通讯作者：
Jin-qing Liu;Jianmin Zhu;Aiyan Hu;A. Zhang;Chunbaixue Yang;Jianyu Yu;K. Ghoshal;S. Basu;X. Bai
中科院分区：
文献类型：
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作者：
Jin-qing Liu;Jianmin Zhu;Aiyan Hu;A. Zhang;Chunbaixue Yang;Jianyu Yu;K. Ghoshal;S. Basu;X. Bai
细胞因子是最早用于人类癌症试验的免疫治疗药物之一，并取得了显着成功。然而，由于其显著的毒性和通常缺乏疗效，细胞因子已经将其聚光灯投向其他癌症免疫治疗剂，如免疫检查点抑制剂。然而，只有一部分癌症患者对检查点抑制剂有反应。因此，开发一种新的基于精氨酸的免疫疗法仍然是必要的。在一系列候选细胞因子中，IL-27是一种独特的候选细胞因子，具有明显的抗肿瘤活性和低毒性。通过腺相关病毒（AAV-IL-27）全身递送的IL-27被小鼠非常好地耐受，并且在多种肿瘤模型中表现出有效的抗肿瘤活性。AAV-IL-27通过直接刺激免疫效应细胞和全身性消耗T细胞来发挥其抗肿瘤活性，并且特别适合与检查点抑制剂或疫苗组合递送。此外，AAV-IL-27还可以局部递送至肿瘤以发挥其独特的作用。在这篇综述中，我们总结了支持这些观点的证据，并提出了AAV递送的IL-27作为一种潜在的癌症免疫原。
Cytokines are one of the first immunotherapeutics utilized in trials of human cancers with significant success. However, due to their significant toxicity and often lack of efficacy, cytokines have given their spotlight to other cancer immunotherapeutics such as immune checkpoint inhibitors. Nevertheless, only a subset of cancer patients respond to checkpoint inhibitors. Therefore, developing a novel cytokine-based immunotherapy is still necessary. Among an array of cytokine candidates, IL-27 is a unique one that exhibits clear anti-tumor activity with low toxicity. Systemically delivered IL-27 by adeno-associated virus (AAV-IL-27) is very well tolerized by mice and exhibits potent anti-tumor activity in a variety of tumor models. AAV-IL-27 exerts its anti-tumor activity through directly stimulation of immune effector cells and systemic depletion of Tregs, and is particularly suitable for delivery in combination with checkpoint inhibitors or vaccines. Additionally, AAV-IL-27 can also be delivered locally to tumors to exert its unique actions. In this review, we summarize the evidence that support these points and propose AAV-delivered IL-27 as a potential immunotherapeutic for cancer.