POLY ICLC AND ALPHA INTERFERON IN REFRACTORY MALIGNANCY

这项试验旨在测试Poly-ICLC和Alpha的组合 干扰素在难治性恶性肿瘤患者中的应用α干扰素 诱导一些干扰素反应基因的合成。这些 诱导基因产物负责产生抗增殖剂 而α干扰素的抗病毒作用是2‘，5’寡腺苷 合成酶和P1/eIF2α激酶。这两种基因产物都是 由阿尔法诱导 干扰素，但需要额外的因素来激活它们。双倍- 链状核糖核酸能够激活2‘，5’ 寡腺苷合成酶和P1/eIF2α激酶。激活 后者与强有力的蛋白质合成抑制有关。激活 后者与强大的蛋白质合成抑制有关。这个 α干扰素和双链核糖核酸的结合 几种人肿瘤细胞株的协同抗增殖作用 包括肺、膀胱和肉瘤。协同的程度从以下几个方面 3-250折。本研究将探讨其毒性、免疫学效应和 α-干扰素与Poly-ICLC联合应用的抗肿瘤活性 每日皮下注射，每周3次肌肉注射， 分别进行了分析。到目前为止，已有17名患者参加了试验。 在最初一周的治疗中，两名患者被排除在研究之外 单独使用α干扰素，1例患者出现IV级肝毒性 第二例患者为III级疲劳。已经有三次了 恶性黑色素瘤患者的部分反应 和两个轻微的反应，一个发生在肾癌患者身上，另一个发生在 在直肠癌患者中排名第二。

This trial was designed to test the combination of Poly-ICLC and alpha interferon in patients with refractory malignancy. Alpha interferon induces the synthesis of a number of interferon responsive genes. These induced gene products are responsible for producing the antiproliferative and antiviral effects of alpha interferon are the 2', 5' oligoadenylate synthetase and the P1/EIF2 alpha kinase. Both of these gene products are induced by alpha interferon but require additional factors to activate them. Double- stranded ribonucleic acid is capable of activating both 2', 5' oligoadenylate synthetase and P1/EIF2 alpha kinase. Activation of the latter is associated with potent protein synthesis inhibition. Activation of the latter is associated with potent protein synthesis inhibition. The combination of alpha interferon and double-stranded ribonucleic acids has synergestic antiproliferative effects in several human tumor cell lines including lung, bladder, and sarcomas. The levels of synergism range from 3-250 fold. This study will explore the toxicity, immunologic effects and antitumor activity of the combination of alpha interferon and Poly-ICLC administered by daily subcutaneous and 3 x weekly intramuscular injection, respectively. To date, seventeen patients have been entered on the trial. Two patients were removed from study during the initial week of therapy with alpha interferon alone, one patient due to Grade IV hepatic toxicity and the second patient due to Grade III fatigue. There have been three responses to date, a partial response in a patient with malignant melanoma and two minor responses, one in a patient with renal cell cancer and a second in a patient with rectal carcinoma.