Wang Peng, Wu Yi, Yang Chen, Zhao Guanan, Liu Yonghua, Cheng Gang, Wang Shibing
Medical Laboratory Center, Lishui City People's Hospital, Lishui, People's Republic of China.
Department of Hematology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China.
Onco Targets Ther. 2020 Feb 17;13:1421-1429. doi: 10.2147/OTT.S209312. eCollection 2020.
Oncolytic virotherapy is a promising alternative to conventional treatment, yet limited viral replication and immune-negative feedback are the major hurdles to effective viro-immunotherapy.
In this study, we found that use of an adjuvant of embelin, a small molecular inhibitor of XIAP, increased the replication of oncolytic vaccinia virus (OVV) by mitigating antiviral innate immunity. Moreover, embelin suppresses constitutive STAT3 phosphorylation and mitigates OVV-induced activation of STAT3 in lymphoma. In the subcutaneous lymphoma model, embelin significantly enhanced the therapeutic efficacy of OVV and prolonged the survival. In addition, embelin significantly increased the OVV-induced infiltration of T cells and NK cells and decreased the number of OVV-induced myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment.
Our results explored the ability of OVV and embelin in combination to enhance lymphoma cell lysis, revealing a beneficial combinatorial effect wherein both lymphoma cell lysis and OVV replication were enhanced both in vitro and in an in vivo murine model system.
Our findings indicate the utility of embelin as an adjuvant for oncolytic viro-immunotherapy.
溶瘤病毒疗法是传统治疗的一种有前景的替代方法，但病毒复制受限和免疫负反馈是有效的病毒免疫疗法的主要障碍。
在本研究中，我们发现使用XIAP的小分子抑制剂紫铆因作为佐剂，通过减轻抗病毒固有免疫来增加溶瘤痘苗病毒（OVV）的复制。此外，紫铆因抑制组成性STAT3磷酸化，并减轻OVV诱导的淋巴瘤中STAT3的激活。在皮下淋巴瘤模型中，紫铆因显著增强了OVV的治疗效果并延长了生存期。此外，紫铆因显著增加了OVV诱导的肿瘤微环境中T细胞和NK细胞的浸润，并减少了OVV诱导的髓源性抑制细胞（MDSC）的数量。
我们的结果探索了OVV与紫铆因联合增强淋巴瘤细胞裂解的能力，揭示了一种有益的联合效应，即在体外和体内小鼠模型系统中，淋巴瘤细胞裂解和OVV复制均得到增强。
我们的研究结果表明紫铆因作为溶瘤病毒免疫疗法佐剂的效用。
