Marincola F M, Drucker B J, Keeling C A, Siao D Y, Starnes H F, Goodwin D A, Holder W D
Department of Surgery, Stanford University School of Medicine, Calif.
Surgery. 1989 Jan;105(1):79-85.
In this study we evaluated human pancreatic cancer xenotransplanted into nude mice as a model suitable for adoptive immunotherapy studies. A pancreatic cancer cell line (MIA PaCa-2) was chosen and its growth in nude mice and sensitivity to lysis by human lymphokine-activated killer (LAK) cells were characterized. This line grew in 96% of the cases when young (4- to 6-week-old) Swiss/NIH nude mice were used. The line was highly sensitive to lysis by LAK cells in a standard chromium-51 release assay (67.8%), similarly to other cell lines known to be highly sensitive, such as K562 (75.6%) and the melanoma cell line SU.102 (53.1%). To assess their in vivo distribution, human peripheral blood lymphocytes (PBLs) and LAK cells were adoptively transferred into nude mice after labeling with indium-111 oxine. The results of this study show that adoptively transferred PBLs and LAK cells localize in this heterologous system as they do in autologous systems. PBLs are taken up mostly by the liver and spleen. The percentage of the administered dose of radioactivity taken up corrected by weight (percent dose per gram tissue) is 64.3 +/- 15.6%d/gm (liver) and 43.5 +/- 9.5%d/gm (spleen). LAK cells are taken up by liver (43.2 +/- 5.3%d/gm) and spleen (28.0 +/- 4.9%d/gm) but also localize significantly more than PBLs in other organs such as lungs (12.9 +/- 3.5%d/gm vs 1.4 +/- 0.3%d/gm, p less than 0.01), kidneys (19.1 +/- 2.1%d/gm vs 6.3 +/- 1.5%d/gm, p less than 0.001), and pancreatic tumors growing in orthotopic position (1.93 +/- 0.36%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.05). When the nude mice are pretreated with human recombinant tumor necrosis factor, localization of LAK cells compared with PBLs is even further enhanced both in tumors implanted in the pancreas (3.1 +/- 0.5%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.01) and in the subcutis (12.5 +/- 8.3%d/gm vs 0.95 +/- 0.29%d/gm, p less than 0.001).
在本研究中，我们评估了异种移植到裸鼠体内的人胰腺癌，将其作为适合过继性免疫治疗研究的模型。选择了一种胰腺癌细胞系（MIA PaCa - 2），并对其在裸鼠体内的生长情况以及对人淋巴因子激活的杀伤细胞（LAK细胞）裂解的敏感性进行了表征。当使用年幼（4至6周龄）的瑞士/美国国立卫生研究院裸鼠时，该细胞系在96%的情况下能够生长。在标准的铬 - 51释放试验中，该细胞系对LAK细胞的裂解高度敏感（67.8%），与其他已知高度敏感的细胞系类似，如K562（75.6%）和黑色素瘤细胞系SU.102（53.1%）。为了评估它们在体内的分布情况，用人铟 - 111奥克辛标记人外周血淋巴细胞（PBLs）和LAK细胞后，将其过继转移到裸鼠体内。本研究结果表明，过继转移的PBLs和LAK细胞在这个异种系统中的定位与在自体系统中一样。PBLs主要被肝脏和脾脏摄取。按体重校正后摄取的放射性给药剂量百分比（每克组织的剂量百分比）在肝脏中为64.3±15.6%d/gm，在脾脏中为43.5±9.5%d/gm。LAK细胞被肝脏（43.2±5.3%d/gm）和脾脏（28.0±4.9%d/gm）摄取，但在其他器官中的定位也明显多于PBLs，如肺（12.9±3.5%d/gm对1.4±0.3%d/gm，p<0.01）、肾脏（19.1±2.1%d/gm对6.3±1.5%d/gm，p<0.001）以及原位生长的胰腺肿瘤（1.93±0.36%d/gm对0.56±0.06%d/gm，p<0.05）。当用重组人肿瘤坏死因子对裸鼠进行预处理时，与PBLs相比，LAK细胞在胰腺植入肿瘤（3.1±0.5%d/gm对0.56±0.06%d/gm，p<0.01）和皮下组织（12.5±8.3%d/gm对0.95±0.29%d/gm，p<0.001）中的定位进一步增强。
