Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom
Clin Sci (Lond). 2019 Jan 18;133(2):181-193. doi: 10.1042/CS20181003. Print 2019 Jan 31.
Cancer treatments often reach a refractory period leading to treatment failure and patients developing disease recurrence. This can be due to tumour cells escaping the immune response and creating an immunosuppressive microenvironment enhancing cancer progression. Immunotherapy has become a promising tool for cancer treatment as it restores the anti-tumour response of the patient's immune system. Immune checkpoint inhibitors are the most widely studied immunotherapies worldwide and are now approved for multiple cancers. However, chimeric antigen receptor (CAR)-T cell therapy has also shown promise by targeting T lymphocytes that are genetically modified to express CARs and this is now approved to treat some haematological cancers. Although immunotherapy has shown successful treatment outcomes in multiple cancers, some patients do not respond to this treatment. Therefore, approaches to enhance the efficacy of immunotherapies are likely to be the key to improve their effectiveness. Therefore, combination therapies of checkpoint inhibitors +/- chemotherapy are at the forefront of current research. Furthermore, biomarkers that predict treatment response are now beginning to emerge. Additionally, utilising nanoparticles as a newly targeted drug delivery system to enhance CAR-T cell therapy may enhance the efficacy of the cells when re-infused within the patient. Even if efficacy is enhanced, severe immune-related adverse events (irAEs) occur that are life-threatening and could lead to therapy being stopped. Therefore, predictive biomarkers for toxicity are also needed to improve both the patient's quality of life and treatment outcomes. This review will look at the current immunotherapies in clinical trials and discuss how to enhance their efficacy.
癌症治疗常常会进入难治期,导致治疗失败和疾病复发。这可能是由于肿瘤细胞逃避了免疫反应,并产生了抑制免疫的微环境,从而促进了癌症的进展。免疫疗法已成为癌症治疗的一种有前途的手段,因为它恢复了患者免疫系统的抗肿瘤反应。免疫检查点抑制剂是全球研究最广泛的免疫疗法,现已批准用于多种癌症。然而,嵌合抗原受体 (CAR)-T 细胞疗法也通过靶向经过基因修饰以表达 CAR 的 T 淋巴细胞显示出了希望,现已批准用于治疗一些血液系统癌症。尽管免疫疗法在多种癌症中显示出了成功的治疗效果,但有些患者对此治疗没有反应。因此,提高免疫疗法疗效的方法可能是提高其有效性的关键。因此,检查点抑制剂 +/- 化疗的联合疗法是当前研究的前沿。此外,预测治疗反应的生物标志物现在也开始出现。此外,利用纳米颗粒作为一种新的靶向药物递送系统来增强 CAR-T 细胞疗法,可能会增强细胞在重新输注到患者体内时的疗效。即使疗效得到增强,也会发生严重的免疫相关不良反应 (irAEs),这些反应可能危及生命,并导致治疗停止。因此,还需要预测毒性的生物标志物,以提高患者的生活质量和治疗效果。本文综述了目前临床试验中的免疫疗法,并讨论了如何增强其疗效。