一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Calcium Electrochemotherapy and Challenges in Combined Treatment with Dendritic Cell Vaccination.
Calcium Electrochemotherapy and Challenges in Combined Treatment with Dendritic Cell Vaccination.
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在本研究中,我们考察了钙基电化学疗法(CaECT,1.3 kV/cm × 100 µs,以1 Hz重复频率递送八个脉冲)与树突状细胞疫苗(DCV)的联合效果。使用Lewis肺癌(LLC1)作为肿瘤模型。我们表征了单独CaECT以及与DCV治疗联合对肿瘤生长的影响,分析了免疫细胞亚群的变化,并研究了第10、20和30天的体液免疫反应动态。鉴于DCV效果有限,我们使用具有已知免疫调节特性的化疗药物环磷酰胺(CP)进行了额外实验。
尽管CaECT表现出强效抗肿瘤活性并诱导了显著的免疫反应,但其与DCV联合并未增强治疗效果。CP联合也未能改善中位生存期。
CaECT是涉及博来霉素或顺铂的标准ECT的一种有前景的替代方案。然而,需要进一步优化以增强CaECT与DCV联合时的治疗协同作用。
Background/Objectives: Electrochemotherapy (ECT) is a reliable and potent technique for managing primary tumors; however, significant efforts are being made to characterize and improve the systemic immune response, which is crucial for metastasis prevention. Current evidence suggests that the advancement of ECT will depend on its integration with complementary immunomodulatory methods.
Methods: In this study, we examined the combined effects of calcium-based electrochemotherapy (CaECT, 1. 3 kV/cm × 100 µs, eight pulses delivered at 1 Hz repetition frequency) with dendritic cell vaccination (DCV). Lewis lung carcinoma (LLC1) was used as a tumor model.
We characterized the effects of CaECT alone and in combination with DCV therapy on tumor growth, analyzed the changes in immune cell subpopulations, and studied the humoral immune response dynamics on day 10, 20, and 30. Given the limited effect of DCV, additional experiments were conducted with the chemotherapeutic drug cyclophosphamide (CP), known for its immunomodulatory properties.
Results: Although CaECT demonstrated potent antitumor activity and induced a significant immune response, its combination with DCV did not result in enhanced therapeutic efficacy. The combination of CP also failed to improve median survival. Conclusions: It is concluded that CaECT is a promising alternative to standard ECT involving bleomycin or cisplatin.
However, further optimization is necessary to enhance the therapeutic synergy of CaECT when combined with DCV.
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