Chemo-immonotherapeutic effects of PD-L1-targeted antibody-catalyst conjugate plus DOX prodrug in a mouse model of colon cancer. Chemo-immonotherapeutic effects of PD-L1-targeted antibody-catalyst conjugate plus DOX prodrug in a mouse model of colon cancer

We designed a study to investiagate chemo-immunotheraputic effect using a mouse model of colon cancer. To investigate the anti-tumor effect of the combination therapy, the in vivo antitumor activities of different mono- and combinational therapy were subsequently evaluated using a C57BL/6J mouse model bearing MC38 tumors. Subcutaneous injection of 1×106 of MC38 cells in the right flank of a mouse was performed 9 days before therapy. The Ru-PD-L1 was administrated by intraperitoneal injection, while the DPD or DOX was given by peritumoral injection. For combinational treatment, each mouse was treated with 14 µg DPD or DOX (0.56 mg/kg) 6 hours after administering 20 ug Ru-PD-L1 (0.80mg/kg). For monotherapy, each mouse was treated with Ru-PD-L1, DPD, or DOX alone. On the 20th day, the mice were sacrificed for tumor collection. The results highlighted that the combination of ACC and DOX prodrug synergistically enhanced immune response and higher antitumor activity compared to the ACC and DOX combination. Overall design: Comparative gene expression profiling analysis of RNA-seq data for (1) Control; (2) DOX; (3) DPD; (4) Ru-PD-L1; (5) Ru-PD-L1+DOX; (6) Ru-PD-L1+DPD treated tumor bearing mice.

本研究旨在通过结直肠癌小鼠模型探究化学免疫治疗的疗效。为明确联合疗法的抗肿瘤效果，本研究后续以携带MC38肿瘤的C57BL/6J小鼠为模型，评估不同单药及联合治疗方案的体内抗肿瘤活性。于治疗前9天，向小鼠右侧肋腹部皮下接种1×10^6个MC38肿瘤细胞。Ru-PD-L1采用腹腔注射给药，DPD或DOX则采用瘤周注射给药。联合治疗组小鼠先以20 μg Ru-PD-L1（0.80 mg/kg）给药，6小时后再给予14 μg DPD或DOX（0.56 mg/kg）。单药治疗组小鼠则分别单独给予Ru-PD-L1、DPD或DOX。于治疗第20天，处死小鼠并收集肿瘤组织。研究结果显示，相较于ACC与DOX的联合方案，ACC与DOX前药的联合疗法可协同增强免疫应答并展现出更高的抗肿瘤活性。实验总体设计：对6组荷瘤小鼠的RNA测序（RNA-seq）数据进行比较基因表达谱分析，各组分别为：(1) 对照组；(2) DOX单药治疗组；(3) DPD单药治疗组；(4) Ru-PD-L1单药治疗组；(5) Ru-PD-L1联合DOX治疗组；(6) Ru-PD-L1联合DPD治疗组。