下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells.
免疫治疗是治疗骨肉瘤(OS)的一种有吸引力的治疗策略。
免疫治疗是治疗骨肉瘤(OS)的一种有吸引力的治疗策略。γδ T 细胞的独特特征使其在癌症免疫治疗中广受欢迎。在此,我们利用人外周血单个核细胞(PBMCs)扩增了 γδ T 细胞,并研究了它们对 OS 细胞的治疗潜力。来自健康供体的 PBMCs 用 CON 培养基(未刺激对照);EX 培养基,即 CON 加重组人白细胞介素-2(rhIL-2)和唑来膦酸;以及 EX28 培养基,即 CON 加 rhIL-2、唑来膦酸和 CD3/CD28 激活剂,培养 10 天。扩增的 γδ T 细胞通过磁性细胞分离或荧光激活细胞分选进行分离,与两种 OS 细胞系(KHOS/NP 和 MG-63)以不同细胞比例培养,联合或不联合多柔比星或异环磷酰胺,并分析细胞毒性和细胞因子分泌。CD3 + γδTCR + Vγ9 + 三阳性 γδ T 细胞的数量以及 IFN-γ 和 TNF-α 的浓度在补充 rhIL-2(100 IU)和唑来膦酸(1 μM)的培养条件中最高。CD3/CD28 激动剂对 γδ T 细胞扩增未显示出任何额外效果。扩增的 γδ T 细胞以比例和时间依赖的方式对 OS 表现出强效的体外细胞毒性。γδ T 细胞可能增强化疗药物对 OS 的效果,并可能成为 OS 的一种新治疗策略,包括化学免疫治疗。
Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3 + γδTCR + Vγ9 + triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 μM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.
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