Yang Yuanzheng, Zhou Yifan, Wang Jian, Zhou You, Watowich Stephanie S, Kleinerman Eugenie S
Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Department of Immunology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cancers (Basel). 2024 Sep 24;16(19):3251. doi: 10.3390/cancers16193251.
We generated a CD103DC 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.
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 the and tumor 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 of cDCV therapy against lung 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.
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.
cDCV 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. cDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients.
我们使用K7M3骨肉瘤细胞裂解物制备了一种CD103树突状细胞疫苗（cDCV），并研究了其诱导原发性肿瘤消退、已形成的肺转移灶消退以及全身免疫反应的能力。
采用双侧肿瘤模型评估cDCV治疗效果和全身免疫诱导情况。将K7M3细胞双侧注射到小鼠体内。右侧肿瘤接受PBS（对照）或cDCV治疗。左侧肿瘤不进行处理。比较对侧治疗侧和未治疗侧肿瘤的生长情况，并与对照组进行比较。评估肿瘤、肿瘤引流淋巴结（TdLNs）和脾脏的免疫细胞谱。为确定cDCV治疗对肺转移灶的疗效，将K7M3细胞经胫骨内注射。5周后进行截肢手术。小鼠静脉注射PBS或cDCV，6周后安乐死。收集肺、TdLNs和脾脏。对肺结节的数量和大小进行量化。还评估肿瘤、淋巴结和脾脏的免疫细胞谱。使用同一模型，我们评估了cDCV + 抗CTLA-4的效果。
与对照治疗的小鼠相比，cDCV治疗抑制了治疗侧和未治疗侧的肿瘤，并增加了这些肿瘤和淋巴结中T细胞的数量。截肢后进行全身cDCV治疗可减小肺转移灶的大小和数量，并增加肿瘤和淋巴结中T细胞的数量。将抗CTLA-4与cDCV治疗联合使用可提高cDCV对肺转移灶的疗效。
cDCV产生了全身免疫反应，抑制了治疗侧和未治疗侧肿瘤的生长，肿瘤和淋巴结中的T细胞数量增加。cDCV对已形成的肺转移灶有效。抗CTLA4可提高疗效。cDCV可能为复发/转移性骨肉瘤患者提供一种新的治疗方法。
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