Vaage J
Cancer Res. 1987 Aug 15;47(16):4296-8.
The therapeutic effects of 12 daily peritumor injections of from 100 to 300,000 units of recombinant human interleukin-2 were tested against the syngeneic, immunogenic mammary carcinoma MC2 implanted s.c. into C3H/He mice. Local therapeutic effect on injected tumors was observed down to 300 units of interleukin-2 per injection. Cures of injected tumors were obtained with 1,000 units and more per injection. Systemic therapeutic effect on contralateral, uninjected tumors in treated mice was discernible at 5,000 units and more per injection. Hepatic periportal cellular swelling with mononuclear infiltration, and renal tubular edema were observed at 7,000 units or more per injection. Hepatic and renal repairs were rapid and complete with 50,000 units and less per injection. Hepatic necrosis developed above 50,000 units per injection. Deaths resulted from 100,000 units and more per injection. It is concluded that interleukin-2 can be a safe and effective therapeutic agent at a wide range of doses well below those that may be expected to have serious negative side effects.
对皮下植入C3H/He小鼠的同基因免疫原性乳腺癌MC2,测试了每天在肿瘤周围注射12次、剂量为100至300,000单位重组人白细胞介素-2的治疗效果。观察到每次注射低至300单位白细胞介素-2时对注射肿瘤的局部治疗效果。每次注射1,000单位及以上可使注射肿瘤治愈。每次注射5,000单位及以上时,可观察到对治疗小鼠对侧未注射肿瘤的全身治疗效果。每次注射7,000单位及以上时,观察到肝门周围细胞肿胀伴单核细胞浸润以及肾小管水肿。每次注射50,000单位及以下时,肝脏和肾脏的修复迅速且完全。每次注射超过50,000单位时会发生肝坏死。每次注射100,000单位及以上会导致死亡。得出的结论是,白细胞介素-2在远低于可能预期会产生严重负面副作用的剂量范围内可以是一种安全有效的治疗剂。