Itoh T, Sakata Y, Yoshida Y, Tsushima K, Suzuki H, Saitoh S, Tamura Y, Ogasawara H, Sugimoto N, Takemori H
First Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
Cancer Immunol Immunother. 1990;32(2):88-94. doi: 10.1007/BF01754204.
We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.
我们之前曾报道，在携带MethA肿瘤的小鼠中，小鼠重组干扰素β（Mu-rIFNβ）与小鼠重组干扰素γ（Mu-rIFNγ）联合使用比单独使用其中任何一种对肿瘤生长的抑制作用更强。在本研究中，我们检测了在携带同基因MethA纤维肉瘤的BALB/c小鼠中，向Mu-rIFNβ与Mu-rIFNγ的联合用药中添加人重组白细胞介素-2（Hu-rIL-2）对肿瘤生长的影响。低剂量的Hu-rIL-2（5×10³ U或5×10⁴ U，间隔3天给药）未显示出抗肿瘤活性，而高剂量的Hu-rIL-2（5×10⁵ U）则显示出显著的生长抑制作用。除了IFNβ和IFNγ联合用药外，给予IL-2（剂量范围为5×10³ U至5×10⁵ U）显示出更强的抗肿瘤作用，且呈剂量依赖性。此外，与干扰素和IL-2的序贯给药相比，同时给予IL-2、IFNβ和IFNγ具有更有效的治疗活性。这些发现表明，IL-2与IFNβ和γ联合使用对癌症治疗有效。
