POLY ICLC AND ALPHA INTERFERON IN REFRACTORY MALIGNANCY

干扰素可诱导大量基因产物的合成。这些 产品在抗病毒和抗增殖作用中发挥作用 阿尔法干扰素。两种诱导基因产物，2‘，5’-寡腺苷 合成酶和双链抑制物(DSI)是由 干扰素，但需要双链RNA来激活它们。DSI 在抑制蛋白质合成启动中起主要作用 真核细胞起始因子2(eIF-2)在丝氨酸51上的磷酸化 它的阿尔法亚单位。 这项研究联合使用干扰素α和Poly ICLC，a 双链RNA的形式，以确定最佳剂量水平 干扰素诱导DSI及Poly ICLC的最佳剂量 用于激活该激活酶。三个剂量水平的干扰素是 与Poly ICLC的四个剂量水平之一相结合。 这项研究旨在确定这种组合的毒性和 最大耐受量。观察了剂量限制性毒性 干扰素10mU/m2联合Poly ICLC 0.03 mg/m2。毒性 包括长期低血压，需要住院治疗 静脉输液。允许更高剂量的Poly ICLC 在不使用干扰素的情况下，以10mU/m2剂量水平给予干扰素 毒性。这些结果表明，在较低的浓度下，Poly ICLC的毒性可能更大 剂量或更高剂量的ICLC可能会降低干扰素的毒性。

Interferon induces the synthesis of a large number of gene products. These products play a role in the antiviral and antiproliferative effects of alpha interferon. Two of the induced gene products, 2',5'-oligoadenylate synthetase and the double-stranded inhibitor (DSI) are induced by interferon but require double-stranded RNA to activate them. The DSI plays a major role in inhibiting protein synthesis initiation by phosphorylating the eukaryotic initiation factor 2 (eIF-2) on serine 51 of its alpha subunit. This study combined administration of interferon alpha and Poly ICLC, a form of double-stranded RNA, in order to determine the optimal dose level of interferon for induction of the DSI and the optimal dose of Poly ICLC for activation of the kinase. Three dose levels of interferon were combined with one of four dose levels of Poly ICLC. This study was designed to determine the toxicity of this combination and the maximal tolerated dose. Dose-limiting toxicity was observed with the combination of interferon 10 mu/m2 and Poly ICLC 0.03 mg/m2. Toxicity consisted of prolonged hypotension requiring hospitalization for intravenous fluid administration. Higher doses of Poly ICLC allowed administration of interferon at the 10 mu/m2 dose level without this toxicity. These results suggest that Poly ICLC may be more toxic at lower doses or that higher doses of ICLC may reduce the toxicity of interferon.