Thompson J A, Lee D J, Lindgren C G, Benz L A, Collins C, Shuman W P, Levitt D, Fefer A
Department of Medicine, School of Medicine, University of Washington, Seattle 98195.
Cancer Res. 1989 Jan 1;49(1):235-40.
The purpose of this study was to compare the toxicity, immunomodulatory changes, and antitumor efficacy of interleukin 2 (IL-2) and lymphokine activated killer (LAK) cell therapy with two durations of IL-2 infusion. Patients with progressive melanoma, non-Hodgkin's lymphoma, renal carcinoma, or colon carcinoma received IL-2 at 3 X 10(6) units/m2/day on days 1-5 and 13-17, either by bolus injection every 8 h (q8h) or by continuous i.v. (CIV) administration. Peripheral blood mononuclear cells were harvested by leukapheresis on days 8, 9, and 10, were incubated in vitro for 5 days for generation of LAK cells, and were infused on days 13, 14, and 15. The first 11 patients were treated with IL-2 q8h, and the subsequent 13 patients were treated by CIV infusion. Toxicity consisted primarily of fever, chills, emesis, diarrhea, weight gain, and edema but did not require intensive care unit support and did not differ significantly between treatment groups. IL-2-induced lymphocytosis on day 8 was higher with CIV than with q8h administration with a mean lymphocyte count/microliter of 5610 +/- 700 (SE) versus 3300 +/- 500. Immunomodulatory changes observed on days 8 and 20 were also greater with CIV IL-2 and included an increase in peripheral blood mononuclear cell IL-2 receptor expression as well as a marked rise in the number of Leu-11+ and Leu-19+ peripheral blood mononuclear cells. The total leukapheresis yield per patient and total number of LAK cells infused per patient were higher with CIV than q8h administration, with 49.8 +/- 4.9 X 10(9) versus 39.4 +/- 5.4 X 10(9) and 42.6 +/- 5.0 X 10(9) versus 34.0 +/- 5.4 X 10(9), respectively. The cells infused displayed phenotypic evidence of activation and exhibited marked lytic reactivity to Daudi, Raji, and HT-144 targets. One complete and one minimal response were observed in 2 of 8 patients with metastatic renal cell carcinoma who received CIV IL-2 and LAK cells. The results show that IL-2 is more biologically active by CIV than q8h administration, as demonstrated by greater rebound lymphocytosis, LAK cell yield, and in vivo immunostimulation.
本研究的目的是比较白细胞介素2（IL-2）和淋巴因子激活的杀伤细胞（LAK）疗法在两种IL-2输注持续时间下的毒性、免疫调节变化和抗肿瘤疗效。进展期黑色素瘤、非霍奇金淋巴瘤、肾癌或结肠癌患者在第1 - 5天和第13 - 17天接受3×10⁶单位/m²/天的IL-2治疗，给药方式为每8小时一次推注（q8h）或持续静脉输注（CIV）。在第8、9和10天通过白细胞分离术采集外周血单个核细胞，在体外培养5天以生成LAK细胞，并在第13、14和15天进行输注。前11例患者接受IL-2 q8h治疗，随后的13例患者接受CIV输注。毒性主要包括发热、寒战、呕吐、腹泻、体重增加和水肿，但不需要重症监护病房支持，且治疗组之间无显著差异。第8天时，CIV给药组IL-2诱导的淋巴细胞增多高于q8h给药组，平均淋巴细胞计数/微升分别为5610±700（SE）和3300±500。在第8天和第20天观察到的免疫调节变化在CIV IL-2组中也更大，包括外周血单个核细胞IL-2受体表达增加以及Leu-11⁺和Leu-19⁺外周血单个核细胞数量显著增加。CIV给药组每位患者的白细胞分离术总产量和输注的LAK细胞总数均高于q8h给药组，分别为49.8±4.9×10⁹和39.4±5.4×10⁹，以及42.6±5.0×10⁹和34.0±5.4×10⁹。输注的细胞显示出激活的表型证据，并对Daudi、Raji和HT - 144靶标表现出明显的溶解反应性。在接受CIV IL-2和LAK细胞治疗的8例转移性肾细胞癌患者中有2例观察到1例完全缓解和1例微小缓解。结果表明，CIV给药时IL-2的生物活性高于q8h给药，表现为更强的反弹性淋巴细胞增多、LAK细胞产量和体内免疫刺激。
