INVIVO ANTITUMOR-ACTIVITY OF COMBINATIONS OF INTERFERON-ALPHA AND INTERLEUKIN-2 IN A MURINE MODEL - CORRELATION OF EFFICACY WITH THE INDUCTION OF CYTOTOXIC-CELLS RESEMBLING NATURAL-KILLER-CELLS
INVIVO ANTITUMOR-ACTIVITY OF COMBINATIONS OF INTERFERON-ALPHA AND INTERLEUKIN-2 IN A MURINE MODEL - CORRELATION OF EFFICACY WITH THE INDUCTION OF CYTOTOXIC-CELLS RESEMBLING NATURAL-KILLER-CELLS
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DOI：
10.1002/ijc.2910400314
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发表时间：
1987-09-15
影响因子：
6.4
通讯作者：
SULICH, V
中科院分区：
文献类型：
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作者：
BRUNDA, MJ;BELLANTONI, D;SULICH, V
2种重组细胞因子白介素-2（rIL-2）和人杂合干扰素α（rHuIFN-α）的体内抗肿瘤活性在体外进行了研究。D），使用鼠网状细胞肉瘤M5076进行测试。静脉注射肿瘤细胞后的实验性肝转移，以及皮下注射肿瘤细胞后的肿瘤生长和自发转移。注射肿瘤细胞，在用这些细胞因子的组合处理的小鼠中比在用任一种单独处理的动物中受到更大程度的抑制。当与外科手术切除s.c.肿瘤，用两种细胞因子治疗小鼠显著延长了荷瘤动物的存活。用细胞因子的组合注射正常小鼠，但不单独注射任何一种细胞因子，导致肝效应细胞的细胞毒活性显著增加。这些小鼠中的效应细胞似乎是NK细胞，因为这种增强的细胞毒性在用抗脱唾液酸GM 1体内治疗的动物或NK缺陷的米色小鼠中显著降低。此外，在用这些细胞因子处理的携带M5076的米色小鼠中未观察到体内功效。因此，用rIL-2和rHuIFN-α A/D注射小鼠导致肝脏中NK细胞样群体的诱导，其具有增强的细胞毒性活性，这与在该鼠模型中观察到的体内抗肿瘤活性相关。这些结果表明细胞因子，特别是IFN-α，和IL-2可以有效地组合用于治疗肿瘤和/或转移。
The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-.ALPHA./D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-.alpha.A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-.alpha. and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.