Naruo K I, Hinuma S, Shiho O, Houkan T, Ootsu K, Tsukamoto K
Biotechnology Laboratories, Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Clin Exp Immunol. 1989 May;76(2):278-83.
When Meth-A fibrosarcoma-bearing BALB/c mice were injected subcutaneously with 10 micrograms of recombinant human interleukin 2(rIL-2) once a day for 10 days, tumour growth inhibition was in the range of 22-31% of that of the control animals. Anti-tumour effector cells against Meth-A were detected in the spleen cells of the tumour-bearing BALB/c mice injected with rIL-2, using a modified Winn-type neutralization assay with the auxiliary injection of rIL-2. To induce the strongest anti-tumour activity in this assay system, the following were necessary: 1) the effector cells were derived from tumour-bearing BALB/c mice; 2) the donors of the effector cells were injected with rIL-2; 3) the recipient mice in the Winn assay were auxiliarily injected with rIL-2 (a modified Winn assay). The anti-tumour effector activity detected in the modified Winn assay was inhibited by treatment with anti-CD8 or anti-asialo GM1 antibodies plus complement (C), but not completely. We supposed that at least two kinds of anti-Meth-A effector cells with different surface antigens, positive for CD8 and asialo GM1 antigens, were induced in the Meth-A-bearing BALB/c mice injected with rIL-2; these populations seemed to function independently and at least partly as anti-tumour effector cells in this tumour-host system. These spleen cells showed in vitro cytotoxicity against Meth-A cells, which are resistant to NK cells, if the activity was measured in a 24 h 51Cr-release assay in the presence of rIL-2.
将携带Meth-A纤维肉瘤的BALB/c小鼠每天皮下注射10微克重组人白细胞介素2(rIL-2),连续注射10天,肿瘤生长抑制率为对照动物的22%-31%。采用改良的Winn型中和试验并辅助注射rIL-2,在注射rIL-2的携带肿瘤的BALB/c小鼠的脾细胞中检测到针对Meth-A的抗肿瘤效应细胞。为了在该试验系统中诱导最强的抗肿瘤活性,需要以下条件:1)效应细胞来源于携带肿瘤的BALB/c小鼠;2)效应细胞的供体注射rIL-2;3)Winn试验中的受体小鼠辅助注射rIL-2(改良的Winn试验)。改良的Winn试验中检测到的抗肿瘤效应活性被抗CD8或抗去唾液酸GM1抗体加补体(C)处理所抑制,但未完全被抑制。我们推测,在注射rIL-2的携带Meth-A的BALB/c小鼠中诱导出至少两种具有不同表面抗原的抗Meth-A效应细胞,它们对CD8和去唾液酸GM1抗原呈阳性;在这个肿瘤-宿主系统中,这些细胞群体似乎独立发挥作用,并且至少部分地作为抗肿瘤效应细胞。如果在rIL-2存在的情况下通过24小时51Cr释放试验测量活性,这些脾细胞对NK细胞耐药的Meth-A细胞表现出体外细胞毒性。