Molecular diagnosis laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, PR China; Department of Clinical Medicine, Qingdao University, Qingdao, PR China.
Molecular diagnosis laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, PR China; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310000, PR China.
Biomed Pharmacother. 2021 Jul;139:111573. doi: 10.1016/j.biopha.2021.111573. Epub 2021 Apr 22.
The incidence of hematological malignancies such as multiple myeloma, leukemia, and lymphoma has increased over time. Although bone marrow transplantation, immunotherapy and chemotherapy have led to significant improvements in efficacy, poor prognosis in elderly patients, recurrence and high mortality among hematological malignancies remain major challenges, and innovative therapeutic strategies should be explored. Besides directly lyse tumor cells, oncolytic viruses can activate immune responses or be engineered to express therapeutic factors to increase antitumor efficacy, and have gradually been recognized as an appealing approach for fighting cancers. An increasing number of studies have applied oncolytic viruses in hematological malignancies and made progress. In particular, strategies combining immunotherapy and oncolytic virotherapy are emerging. Various phase I clinical trials of oncolytic reovirus with lenalidomide or programmed death 1(PD-1) immune checkpoint inhibitors in multiple myeloma are ongoing. Moreover, preclinical studies of combinations with chimeric antigen receptor T (CAR-T) cells are underway. Thus, oncolytic virotherapy is expected to be a promising approach to cure hematological malignancies. This review summarizes progress in oncolytic virus research in hematological malignancies. After briefly reviewing the development and oncolytic mechanism of oncolytic viruses, we focus on delivery methods of oncolytic viruses, especially systemic delivery that is suitable for hematological tumors. We then discuss the main types of oncolytic viruses applied for hematological malignancies and related clinical trials. In addition, we present several ways to improve the antitumor efficacy of oncolytic viruses. Finally, we discuss current challenges and provide suggestions for future studies.
随着时间的推移，多发性骨髓瘤、白血病和淋巴瘤等血液系统恶性肿瘤的发病率有所增加。尽管骨髓移植、免疫疗法和化疗已显著提高了疗效，但老年患者预后不良、血液系统恶性肿瘤的复发率和高死亡率仍然是主要挑战，应探索创新的治疗策略。溶瘤病毒不仅可以直接裂解肿瘤细胞，还可以激活免疫反应或被设计表达治疗因子以提高抗肿瘤疗效，逐渐被认为是对抗癌症的一种有吸引力的方法。越来越多的研究将溶瘤病毒应用于血液系统恶性肿瘤并取得了进展。特别是，免疫疗法和溶瘤病毒治疗联合的策略正在出现。多项关于在多发性骨髓瘤中应用溶瘤性呼肠孤病毒联合来那度胺或程序性死亡受体 1（PD-1）免疫检查点抑制剂的 I 期临床试验正在进行中。此外，与嵌合抗原受体 T（CAR-T）细胞联合的临床前研究也在进行中。因此，溶瘤病毒治疗有望成为治疗血液系统恶性肿瘤的一种很有前途的方法。本文综述了溶瘤病毒在血液系统恶性肿瘤中的研究进展。在简要回顾溶瘤病毒的发展和溶瘤机制后，我们重点介绍了溶瘤病毒的递送方法，特别是适用于血液系统肿瘤的全身递送方法。然后我们讨论了应用于血液系统恶性肿瘤的主要溶瘤病毒类型及其相关临床试验。此外，我们还提出了几种提高溶瘤病毒抗肿瘤疗效的方法。最后，我们讨论了当前的挑战并为未来的研究提供了建议。
