| 宣柳,刘增辉,白娟,等.靶向4-1BB抗体ZG-033对小鼠黑色素瘤的抑制作用及其调节机制[J].中国临床保健杂志,2026,29(2):261-266. |
| 靶向4-1BB抗体ZG-033对小鼠黑色素瘤的抑制作用及其调节机制 |
| Inhibitory effect and mechanism of 4-1BB antibody-ZG033 on melanoma mouse model |
| 投稿时间：2025-12-10 |
| DOI：10.3969/J.issn.1672-6790.2026.02.023 |
| 中文关键词: 黑色素瘤 分子靶向治疗 生存时间 疾病模型,动物 |
| 英文关键词: Melanoma Molecular targeted therapy Survival time Disease models,animal Fund programs:Anhui Provincial Health Research Project |
| 基金项目:安徽省卫生健康科研项目 |
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| 中文摘要: |
| 目的 探讨靶向4-1BB(CD137)抗体ZG-033对小鼠黑色素瘤的抑制效果及其调节机制。方法 采用无特定病原体(SPF)级雄性C57BL/6J小鼠构建B16F10黑色素瘤皮下移植瘤模型,7 d后,筛选出30只肿瘤体积相近的小鼠,随机数字表法分为模型组、PD-1组和ZG-033组,同时选取健康的SPF级雄性C57BL/6J小鼠作为对照组。测量肿瘤生长体积,酶联免疫吸附法(ELISA)检测血清白细胞介素(IL)-2、干扰素(IFN)-γ水平,用流式细胞术检测CD8+ T淋巴细胞、中央记忆型T细胞(Tcm)在脾组织中占比,免疫荧光检测肿瘤组织CD8+浸润数量,绘制小鼠生存曲线图。结果 与模型组相比,ZG-033组小鼠的血清IL-2和IFN-γ水平升高,脾组织中的Tcm比例增加,肿瘤组织CD8+T细胞浸润数量增加,小鼠生存时间延长,差异均有统计学意义(P<0.05)；ZG-033组疗效优于PD-1组,组间差异有统计学意义(P<0.05)。结论 ZG-033抗体治疗通过阻断免疫共刺激分子作用,促进细胞因子分泌,上调脾组织中Tcm的比例,增强肿瘤组织中CD8+T细胞的浸润,抑制荷瘤小鼠的肿瘤生长,有效延长荷瘤小鼠的生存时间。 |
| 英文摘要: |
| Objective To explore the inhibitory effect of the previously developed 4-1BB (CD137) antibody ZG033 on mouse melanoma and its immunomodulatory mechanisms.Methods Thirty specific pathogen-free (SPF) male C57BL/6J mice were used to establish subcutaneous transplanted tumor models with B16F10 melanoma cells.Seven days later,30 mice with comparable tumor volumes were selected and randomly divided using a random number table into a model group,a PD-1 group,and a ZG-033 group.Additionally,healthy SPF male C57BL/6J mice were selected as the control group.Tumor growth volume was measured,serum levels of IL-2 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA),the proportions of CD8+T lymphocytes and central memory T cells (Tcm) in the spleen were measured by flow cytometry,CD8+T cell infiltration in tumor tissues was detected by immunofluorescence,and mouse survival curves were plotted.Results ZG-033 antibody treatment significantly inhibited tumor growth in tumor-bearing mice and improved multiple immune-related indicators.Compared to the model group,mice in the ZG-033 group exhibited significantly increased serum levels of IL-2 and IFN-γ,a substantially higher proportion of central memory T cells in the spleen,a marked rise in tumor-infiltrating CD8+T cell numbers,and significantly prolonged survival time,with all differences being statistically significant (P<0.05).Furthermore,in all the aforementioned indicators,the ZG-033 group demonstrated superior outcomes compared to the PD-1 monotherapy group,and the intergroup differences were also statistically significant (P<0.05).Conclusions ZG-033 antibody,by mediating co-stimulatory signals,significantly promotes cytokine secretion,upregulates the proportion of Tcm in the spleen,and enhances the infiltration of CD8+T cells in tumor tissues,thereby overall improving the body′s anti-tumor immune response and effectively extending the survival time of tumor-bearing mice. |
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