Belldegrun A, Uppenkamp I, Rosenberg S A
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
J Urol. 1988 Jan;139(1):150-5. doi: 10.1016/s0022-5347(17)42342-1.
Immunotherapy utilizing the adoptive transfer of lymphokine activated killer (LAK) cells in conjunction with recombinant interleukin-2 (IL-2) is capable of mediating the regression of established cancer in a variety of animal tumor models as well as advanced metastatic cancers in humans. We have thus examined the variability of the anti-tumor lytic reactivity of LAK cells obtained from patients with metastatic renal cell cancer (RCC). Tumor cell suspensions were prepared by enzymatic digestion from 37 consecutive renal cell tumors. The mean (+/- SEM) total number of cells recovered was 1.5 +/- 2.2 X 10(9) cells per tumor. The percentage of tumor cells in the suspension was 39.1 +/- 3.3% (range: 6 to 75%). Thirteen of 13 different fresh renal tumor cell preparations tested in 57 experiments and tow of two renal tumor lines tested in 10 experiments were all lysed by LAK cells. RCC patients, like normal donors, generated good LAK effectors with broad antitumor activity against autologous as well as allogenic tumors. Both renal and nonrenal tumors were equally lysed by LAK cells. LAK killing of the erythroleukemic tumor lines K562 and Daudi was significantly better than the lysis of fresh autologous and allogeneic tumor targets or cultured RCC tumor lines. Short term tumor cultures derived from renal cancer preparations proved to be sensitive and reliable tumor targets for studying the in vitro killing by LAK cells. Clinical trials testing the therapeutic role of LAK cells and IL-2 in patients with advanced renal cell cancer are currently in progress.
利用淋巴因子激活的杀伤细胞(LAK)的过继性转移联合重组白细胞介素-2(IL-2)进行免疫治疗,能够在多种动物肿瘤模型以及人类晚期转移性癌症中介导已形成肿瘤的消退。因此,我们检测了从转移性肾细胞癌(RCC)患者获取的LAK细胞抗肿瘤溶解反应性的变异性。通过酶消化法从37例连续的肾细胞肿瘤制备肿瘤细胞悬液。每个肿瘤回收细胞的平均总数(±标准误)为1.5±2.2×10⁹个细胞。悬液中肿瘤细胞的百分比为39.1±3.3%(范围:6%至75%)。在57次实验中检测的13种不同新鲜肾肿瘤细胞制剂中的13种以及在10次实验中检测的2种肾肿瘤细胞系中的2种,均被LAK细胞溶解。RCC患者与正常供体一样,产生了具有广泛抗肿瘤活性的良好LAK效应细胞,可对抗自体以及同种异体肿瘤。肾肿瘤和非肾肿瘤均被LAK细胞同等程度地溶解。LAK细胞对红白血病肿瘤细胞系K562和Daudi的杀伤明显优于对新鲜自体和同种异体肿瘤靶标或培养的RCC肿瘤细胞系的溶解。源自肾癌制剂的短期肿瘤培养物被证明是用于研究LAK细胞体外杀伤作用敏感且可靠的肿瘤靶标。目前正在进行检测LAK细胞和IL-2在晚期肾细胞癌患者中的治疗作用的临床试验。