A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity
文献类型：期刊论文
| 作者 | Shi, Wenqiang1; Lv, Liangyin1; Liu, Nan2; Wang, Hui1; Wang, Yang1; Zhu, Wen1; Liu, Zexin1; Zhu, Jianwei1; Lu, Huili1 |
| 刊名 | MOLECULAR THERAPY
 |
| 出版日期 | 2023-01-04 |
| 卷号 | 31期号:1页码:66-77 |
| ISSN号 | 1525-0016 |
| DOI | 10.1016/j.ymthe.2022.08.016 |
| 通讯作者 | Lu, Huili(roadeer@sjtu.edu.cn) |
| 英文摘要 | Despite the demonstrated immense potential of immune checkpoint inhibitors in various types of cancers, only a minor-ity of patients respond to these therapies. Immunocytokines designed to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME) and block the immune checkpoint simultaneously may provide a strategic advantage over the combination of two single agents. To increase the response rate to checkpoint blockade, in this study, we developed a novel immunocytokine (LH01) composed of the antibody against programmed death-ligand 1 (PD-L1) fused to interleukin (IL)-15 receptor alpha-sushi domain/IL-15 complex. We demonstrate that LH01 efficiently binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. In syngeneic mouse models, LH01 showed improved antitumor efficacy and safety versus anti-PD-L1 plus LH02 (Fc-sushi-IL15) combination and overcame resistance to anti -PD-L1 treatment. Mechanistically, the dual anti-immunosup-pressive function of LH01 activated both the innate and adaptive immune responses and induced a favorable and im-munostimulatory TME. Furthermore, combination therapy with LH01 and bevacizumab exerts synergistic antitumor ef-fects in an HT29 colorectal xenograft model. Collectively, our results provide supporting evidence that fusion of anti-PD-L1 and IL-15 might be a potent strategy to treat patients with cold tumors or resistance to checkpoint blockade. |
| 资助项目 | Science and Technology Com-mission of Shanghai Municipality[21S11906300] |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:000927833700001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/303297]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lu, Huili |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Engn Res Ctr Cell & Therapeut Antibody, Sch Pharm, Minist Educ, 800 Dongchuan Rd, Shanghai 200240, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shi, Wenqiang,Lv, Liangyin,Liu, Nan,et al. A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity[J]. MOLECULAR THERAPY,2023,31(1):66-77. |
| APA | Shi, Wenqiang.,Lv, Liangyin.,Liu, Nan.,Wang, Hui.,Wang, Yang.,...&Lu, Huili.(2023).A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity.MOLECULAR THERAPY,31(1),66-77. |
| MLA | Shi, Wenqiang,et al."A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity".MOLECULAR THERAPY 31.1(2023):66-77. |
入库方式： OAI收割
来源：上海药物研究所
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