Nakamura O, Shitara N, Matsutani M, Takakura K, Machida H
No To Shinkei. 1982 Mar;34(3):267-73.
Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.
研究了聚肌胞苷酸(用聚L - 赖氨酸和羧甲基纤维素稳定的聚IC)在啮齿动物中的干扰素诱导活性、抗肿瘤活性和毒性。将SD品系大鼠静脉注射聚IC或聚肌胞苷酸。使用口炎病毒通过蚀斑减少法测定大鼠血浆中的干扰素。聚肌胞苷酸注射大鼠的血浆干扰素峰值水平与聚IC注射大鼠一样高,并且在前者中,血浆干扰素的高水平持续4 - 12小时。接下来,给荷脑肿瘤大鼠静脉注射聚肌胞苷酸,并每天观察其死亡情况。每周用1mg/kg的聚肌胞苷酸治疗可增加平均存活时间,尽管聚IC未观察到抗肿瘤作用。聚IC的半数致死量(LD50)值为33.5mg/kg,聚肌胞苷酸的LD50值为18.6mg/kg,对于聚肌胞苷酸给药,在剂量低于1.5mg/kg时未发现明显副作用。在临床试验中,以0.05 - 0.2mg/kg的剂量给9例恶性脑肿瘤患者静脉注射聚肌胞苷酸。(6例为胶质母细胞瘤,1例为星形细胞瘤,2例为室管膜瘤。)2例患者接受聚肌胞苷酸注射1次,2例患者注射2次,2例患者注射3次,3例患者注射超过5次。每次给药间隔为7天。聚肌胞苷酸在所有患者中诱导出高水平的血清干扰素(超过100参考单位/毫升),并且超过100单位/毫升的干扰素水平维持24小时。诱导出的最高干扰素效价为875单位/毫升。最常遇到的毒性反应是发热,所有病例均出现。平均峰值体温升高1.9摄氏度,通常在给药后4 - 8小时出现。1例检测到轻度低血压。3例检测到白细胞减少。这些异常均较轻,且在几天内有所改善。关于聚肌胞苷酸的效果,3例患者出现神经功能改善,其中1例在CT扫描中也显示缓解。