Recombinant cell-penetrating trichosanthin synergizes anti-PD-1 therapy in colorectal tumor
文献类型：期刊论文
| 作者 | Zhang, Meng2,3,4; Liu, Ergang1,4; Chen, Guihua3,5; Tang, Yisi3; Fang, Yuefei4; He, Yang3,6; Zhao, Pengfei3,7; Zheng, Caihong2; Muhitdinov, Bahtiyor3,8; Huang, Yongzhuo3,4,9,10,11
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| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2023 |
| 卷号 | 19期号:6页码:1698-1712 |
| ISSN号 | 1449-2288 |
| 关键词 | Trichosanthin cell -penetrating peptide anti -PD-1 therapy tumor immune microenvironment colorectal cancer |
| DOI | 10.7150/ijbs.81052 |
| 通讯作者 | Liu, Ergang(liuergang@zidd.ac.cn) ; Huang, Yongzhuo() |
| 英文摘要 | Alleviating immunosuppression of the tumor microenvironment is an important strategy to improve immune checkpoint therapy. It is an urgent but unmet need to develop adjuvant therapeutics for assisting the mainstay immunotherapies. Trichosanthin is an approved gynecology drug in China and its immunomodulatory effects have drawn much attention as an old drug for new applications in cancer. In this work, a recombinant cell-penetrating trichosanthin (rTCS-LMWP) was prepared via genetic fusion of a cell-penetrating peptide sequence (LMWP) to trichosanthin aiming to overcome the intratumoral penetration and intracellular delivery challenges. The potential of trichosanthin as an adjuvant therapy was explored, including its effects on tumor cells, antigen-presenting cells, tumor immune microenvironment, and the synergistic effect in combination with anti-PD-1. The results revealed that rTCS-LMWP can stimulate the maturation of dendritic cells via activating the STING-TBK1-IRF3 pathway, repolarize the protumor M2-type macrophages, and upregulate the pro-inflammatory cytokine expression. Moreover, rTCS-LMWP can enhance anti-PD-1 therapeutic efficacy in a CT26-bearing mouse model. The synergistic effect involved the induction of immunogenic cell death in the tumors, the proliferation and functionalization of cytotoxic T cells, and the suppression of the immunosuppressive regulatory T cells. These findings indicate that trichosanthin can be developed as an immunomodulator to facilitate cancer immunotherapy. |
| WOS关键词 | MOLECULAR-WEIGHT PROTAMINE ; DENDRITIC CELLS ; PRODRUG-LIKE ; CANCER ; DELIVERY ; MICROENVIRONMENT ; IMMUNOTHERAPY ; MELANOMA ; LUNG |
| 资助项目 | National Key Research and Development Program of China[2021YFC2400600] ; National Key Research and Development Program of China[2021YFE0103100] ; NFSC[81925035] ; NFSC[82050410361] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800] ; Shanghai SciTech Innovation Initiative[CPAYLJ201901] ; Shanghai SciTech Innovation Initiative[2019B090904008] ; High-level Innovative Research Institute[2021B0909050003] ; Department of Science and Technology of Guangdong Province, Science and Technology Bureau of Zhongshan City ; Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China[LHDMZ23H190002] ; Chinese University of Hong Kong |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| 出版者 | IVYSPRING INT PUBL |
| WOS记录号 | WOS:000981674400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306575]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Ergang; Huang, Yongzhuo |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Zhejiang Univ Sch Med, Womens Hosp, Dept Pharm, Hangzhou 310006, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China 5.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China 6.Zhengzhou Univ, Dept Pharm, Affiliated Hosp 1, Zhengzhou, Peoples R China 7.Zhejiang Univ, Affiliated Hosp 2, Clin Pharmacol Ctr, Sch Med, Hangzhou 310009, Peoples R China 8.Uzbek Acad Sci, Inst Bioorgan Chem, 83 M Ulughbek St, Tashkent 100125, Uzbekistan 9.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China 10.Southern Med Univ, Sch pharmaceut Sci, 1838 Guangzhou Ave North, Guangzhou 510515, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Meng,Liu, Ergang,Chen, Guihua,et al. Recombinant cell-penetrating trichosanthin synergizes anti-PD-1 therapy in colorectal tumor[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023,19(6):1698-1712. |
| APA | Zhang, Meng.,Liu, Ergang.,Chen, Guihua.,Tang, Yisi.,Fang, Yuefei.,...&Huang, Yongzhuo.(2023).Recombinant cell-penetrating trichosanthin synergizes anti-PD-1 therapy in colorectal tumor.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19(6),1698-1712. |
| MLA | Zhang, Meng,et al."Recombinant cell-penetrating trichosanthin synergizes anti-PD-1 therapy in colorectal tumor".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19.6(2023):1698-1712. |
入库方式： OAI收割
来源：上海药物研究所
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