Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. Methods: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between thevaccine-treatedanduntreatedtumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. To determine the efficacy ofsystemiccDCV therapy againstestablishedlung metastases, K7M3 cells were injected intratibially. Leg amputation was performed 5 weeks later. Mice were treated intravenously with PBS or cDCV and euthanized 6 weeks later. Lungs, TdLNs and spleen were collected. The number and size of the lung nodules were quantified. The immune cell profile of tumor, and lymph nodes and spleen were also evaluated. Using this same model, we evaluated the effect of cDCV + anti-CTLA-4. Results: cDCV therapy inhibited the treated and untreated tumors and increased the number of T-cells in these tumors and the lymph nodes compared to control-treated mice. Systemic cDCV therapy administered following amputation decreased the size and number of lung metastases, and increased T-cell numbers in the tumor and lymph nodes. Combining anti-CTLA-4 with cDCV therapy increased cDCV efficacy against lung metastases. Conclusions:IntratumorcDCV generated a systemic immune response inhibiting the growth of both the treated and untreated tumors, with increased T-cells in the tumor and lymph nodes.SystemiccDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients.
背景：我们利用K7M3骨肉瘤细胞裂解物制备了CD103+树突状细胞疫苗（cDCV），并研究其诱导原发肿瘤消退、抑制已形成肺转移灶及激发全身免疫应答的能力。方法：采用双侧肿瘤模型评估cDCV治疗效果及全身免疫诱导作用。在小鼠双侧注射K7M3细胞后，右侧肿瘤接受PBS（对照组）或cDCV治疗，左侧肿瘤不作处理。比较疫苗治疗组对侧未处理肿瘤与对照组肿瘤的生长情况，并评估肿瘤组织、肿瘤引流淋巴结及脾脏的免疫细胞特征。为验证cDCV全身治疗对已形成肺转移灶的疗效，经胫骨注射K7M3细胞5周后实施截肢术，静脉注射PBS或cDCV治疗6周后处死小鼠，收集肺组织、引流淋巴结及脾脏，量化肺结节数量与尺寸，同时评估肿瘤及淋巴器官的免疫细胞特征。基于该模型，我们进一步评估了cDCV联合抗CTLA-4治疗的效果。结果：与对照组相比，cDCV治疗同时抑制了处理侧与未处理侧肿瘤生长，并显著增加肿瘤组织及淋巴结中T细胞数量。截肢后实施的cDCV全身治疗有效减少了肺转移灶的数量与尺寸，同时提升肿瘤及淋巴结中T细胞水平。抗CTLA-4联合cDCV治疗进一步增强了cDCV抑制肺转移的疗效。结论：瘤内注射cDCV可激发全身免疫应答，通过增加肿瘤及淋巴结中T细胞数量，同时抑制处理侧与未处理侧肿瘤生长；全身性cDCV治疗对已形成的肺转移灶具有显著抑制作用，联合抗CTLA-4可增强疗效。cDCV可能为复发/转移性骨肉瘤患者提供新型治疗策略。
CD103+cDC1 Dendritic Cell Vaccine Therapy for Osteosarcoma Lung Metastases
肿瘤(癌症)患者之家