肿瘤生物治疗进展

The work-in-progress in biological cancer therapy

癌症患者急需新型、高效的治疗手段。课题组前期研究集中在包括溶瘤病毒和免疫治疗在内的肿瘤生物治疗,并且首次探明了病毒诱导的线粒体自噬和视黄酸诱导基因I样受体信号通路之间的关系。更重要的是,研究发现溶瘤麻疹病毒减毒疫苗株的溶瘤作用主要是由细胞坏死介导,而非以前研究所认为的细胞凋亡。同时,研究探明了线粒体自噬在细胞凋亡和细胞坏死的转变过程中所起到重要的作用。上述新的发现对于溶瘤免疫治疗的发展是至关重要的。文中就溶瘤病毒与细胞自噬研究进展、免疫诱导三磷酸小干扰RNA研究进展、谷氨酰胺酶在肝癌中的研究进展、纳米材料在对抗肿瘤耐药的应用研究进展进行阐述。

Novel and efficient therapeutic modalities are urgently needed for cancer patients. We focused on biological therapies including oncolytic virotherapy and immune therapy against cancer. In the study of oncolytic virotherapy, we have identified the crosstalk between virus-induced mitophagy and retinoic acid inducible gene I （RIG-I）-like receptors signaling. Importantly, we find that cell necrosis rather than apoptosis （ as supposed by previous studies） contributes dominantly to oncolysis of measles virus Edmon- strain in cancer. Furthermore, we have clarified the role of mitophagy in switching cell death from apoptosis to necrosis. These novel findings are important for further improvement of oncolyticvirotherapy. 5＇-Triphosphate RNA （ppp-RNA） is a specific ligand of the pat- tern recognition receptor retinoic acid-inducible gene I （RIG-I）. By combining immune activation and specific gene silencing, we have designed three anticancer ppp-siRNAs targeting TGF-[3~, GLS1 and VEGF, respectively, and we find that these ppp-siRNAs possess potent antitumor efficacies both in vitro and in vivo. In addition, we have also utilized nanomaterials to treat cancers. Next, we want and try to block the immune escape of cancer by targeting immune checkpoints.