肿瘤细胞治疗研究
英文原题：Quantitative assessment of extravasation of IL-15-secreting MSLN-CAR-NK-92 cells using tumor transparency imaging.
结合这些结果，抗癌免疫细胞的血管外渗效率可被视为评估为靶向胰腺癌的 NK 细胞所设计的 CAR 结构有效性的一个有价值指标。
背景：为提高表达嵌合抗原受体（CAR）的抗癌免疫细胞疗法效果，必须了解抗癌免疫细胞穿出血管的过程。目前尚无研究在显微水平定量评估抗癌免疫细胞从肿瘤血管外渗至肿瘤微环境（TME）的程度。 方法：本研究首次使用肿瘤透明化成像，测定 CAR-NK 与 NK 细胞在胰腺肿瘤中的外渗程度。该成像方法可保留完整血管结构；研究在胰腺癌 NSG 小鼠模型中，准确测量已建立的 MSLN-CAR-NK-92 细胞和未修饰 NK-92 细胞的外渗与浸润。外渗程度通过计算位于肿瘤血管内外的细胞体积比进行量化。 结果：静脉输注后，与 NK-92 细胞相比，MSLN-CAR-NK-92 细胞的外渗率更高（85.3% 对 57.4%）、浸润深度更大（185 m 对 128 m），平均外渗细胞数更多（7,717 对 2,311）。其他浸润和细胞毒性指标也更有利于 MSLN-CAR-NK-92 细胞：CPA50/CPD50 分别为 6,887 个细胞、88 m 和 3,509 个细胞、45 m；CDA50/CDD50 分别为 6,350 个细胞、102 m 和 2,023 个细胞、48 m。上述结果凸显了外渗效率作为评估实体瘤免疫细胞表现指标的价值。 结论：抗癌免疫细胞的外渗效率可作为评估靶向胰腺癌的 NK 细胞 CAR 构建体效果的一项有价值指标。本研究建立了用于评估 CAR-NK 细胞在胰腺癌和胆管癌肿瘤模型中迁移的定量外渗成像平台，为评估免疫细胞递送及其在肿瘤微环境中的治疗分布提供了系统框架。
BACKGROUND: The extravasation of anticancer immune cells is a very important issue that must be understood to improve the anticancer effect of chimeric antigen receptor (CAR)-expressing anticancer immune cell therapy. To date, no study has been reported to quantitatively evaluate the degree of extravasation of anticancer immune cells escaping from tumor blood vessels to the tumor microenvironment (TME) at the microscopic level. METHODS: In this study, for the first time, using tumor transparency imaging, the extent of extravasation of CAR-NK and NK cells in pancreatic tumors was determined. we used tumor transparency imaging, which preserves intact vasculature, to accurately measure the extravasation and infiltration of established MSLN-CAR-NK-92 cells and unmodified NK-92 cells in an NSG mouse model of pancreatic cancer. Extravasation was quantified by calculating the volume ratio of cells located inside versus outside tumor vessels. RESULTS: Following intravenous infusion, MSLN-CAR-NK-92 cells showed higher extravasation rates (85.3% vs. 57.4%), penetration depths (185 m vs. 128 m), and average extravasated cell counts (7,717 vs. 2,311) compared with NK-92 cells. Further measures of penetration and cytotoxicity also favored MSLN-CAR-NK-92 cells, with CPA50/CPD50 values of 6,887 cells at 88 m versus 3,509 cells at 45 m, and CDA50/CDD50 values of 6,350 cells at 102 m versus 2,023 cells at 48 m, respectively. These findings highlight the value of extravasation efficiency as a metric for assessing immune cell performance in solid tumors. CONCLUSION: Considering these results, the extravasation efficiency of anticancer immune cells can be regarded as a valuable indicator for evaluating the effectiveness of CAR constructs designed for NK cells target pancreatic cancer. In this study, we establish a quantitative extravasation imaging platform for evaluating CAR-NK cell trafficking in pancreatic and cholangiocarcinoma tumor models. This approach provides a structured framework for assessing immune cell delivery and therapeutic distribution within the tumor microenvironment.
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