Sondel P M, Kohler P C, Hank J A, Moore K H, Rosenthal N S, Sosman J A, Bechhofer R, Storer B
Department of Pediatrics, University of Wisconsin, Madison 53792.
Cancer Res. 1988 May 1;48(9):2561-7.
Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.
11名患者接受了连续4周的人重组白细胞介素2（IL-2）治疗，每周持续静脉输注4天。测试了两个剂量水平，分别为1×10⁶单位/m²/天和3×10⁶单位/m²/天。大多数患者出现的毒性反应包括发热、寒战、疲劳、贫血、嗜酸性粒细胞增多和肝功能异常。治疗引起的所有副作用均得到缓解，未出现严重或危及生命的问题。治疗4周后可见明显的淋巴细胞增多。在淋巴细胞增多期间获取的新鲜淋巴细胞在体外介导了对一种天然杀伤细胞抗性肿瘤细胞系（Daudi）的增强破坏作用。循环淋巴细胞绝对数量的增加及其介导对Daudi靶细胞直接裂解的能力增强，导致在IL-2治疗结束时细胞毒性潜能平均增加超过100倍。一名接受3×10⁶单位/m²/天治疗的肾癌患者出现了持续可测量的反应，肺部和肝脏转移灶消退超过50%。5名患者接受了第二个疗程的IL-2治疗，为期4周。这5名患者中有4名对该治疗耐受性良好，出现了类似的免疫变化。这些患者未观察到进一步的抗肿瘤反应。因此，一种使用IL-2的耐受性相对良好的免疫治疗方案可使淋巴细胞数量显著增加，并增强其体外抗肿瘤反应性。
