Urba W J, Steis R G, Longo D L, Kopp W C, Maluish A E, Marcon L, Nelson D L, Stevenson H C, Clark J W
Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Cancer Res. 1990 Jan 1;50(1):185-92.
We performed a phase Ia/Ib study of interleukin 2 (IL2) in patients with cancer. Single doses of IL2 from 10(3) units/m2 to 10(7) units/m2 were well tolerated but failed to induce significant immunological changes. Chronic IL2 treatment for 5 days out of 7 for 3 weeks was well tolerated at doses below 10(7) units/m2 and was accompanied by significant immunological changes. Following chronic treatment with intramuscular injections of IL2 at 1 x 10(6) units/m2, we observed augmentation of peripheral blood natural killer activity and induction of peripheral blood LAK activity. Induction of LAK activity was most evident when IL2 was included in the cytotoxicity assay. There was a marked increase in the number of peripheral blood mononuclear cells bearing the Leu-19 marker in association with the observed increases in natural killer and LAK activity. A small percentage of Leu-19+ cells coexpressed CD3. There was heterogeneous expression of the low affinity Fc receptor (CD16). In vivo induced Leu-19+ cells could be divided into two populations, dim and bright, based on the intensity of fluorescent staining with antibodies to Leu-19. The majority of Leu-19 bright cells were CD16- while the majority of Leu-19 dim cells were CD16+. In addition, the intensity of CD16 staining was higher for Leu-19 dim cells than for Leu-19 bright cells. Increases in the amounts of CD38 and CD8 antigens were also observed. Significant increases in serum levels of the soluble IL2 receptor were observed during treatment. One partial remission was noted in a woman with non-Hodgkin's lymphoma.
我们对癌症患者进行了白细胞介素2（IL2）的Ia/Ib期研究。单剂量10³单位/平方米至10⁷单位/平方米的IL2耐受性良好，但未能引起显著的免疫变化。在低于10⁷单位/平方米的剂量下，每周7天中有5天进行为期3周的慢性IL2治疗耐受性良好，并伴有显著的免疫变化。在用1×10⁶单位/平方米的IL2进行肌肉注射慢性治疗后，我们观察到外周血自然杀伤活性增强以及外周血LAK活性的诱导。当IL2包含在细胞毒性试验中时，LAK活性的诱导最为明显。与观察到的自然杀伤和LAK活性增加相关的是，携带Leu-19标记的外周血单核细胞数量显著增加。一小部分Leu-19⁺细胞共表达CD3。低亲和力Fc受体（CD16）存在异质性表达。基于用抗Leu-19抗体进行荧光染色的强度，体内诱导的Leu-19⁺细胞可分为两个群体，即暗群体和亮群体。大多数Leu-19亮细胞为CD16⁻，而大多数Leu-19暗细胞为CD16⁺。此外，Leu-19暗细胞的CD16染色强度高于Leu-19亮细胞。还观察到CD38和CD8抗原量的增加。治疗期间观察到可溶性IL2受体血清水平显著升高。在一名非霍奇金淋巴瘤女性患者中观察到一例部分缓解。
