Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E
Department of Parasitology and Immunology, Okayama University Medical School, Japan.
Cancer Res. 1999 Jul 1;59(13):3128-33.
Immune regulation has been shown to be involved in the progressive growth of some murine tumors. In this study, we demonstrated that a single in vivo administration of an amount less than 0.125 mg of anti-CD25 interleukin 2 receptor alpha monoclonal antibody (mAb; PC61) caused the regression of tumors that grew progressively in syngeneic mice. The tumors used were five leukemias, a myeloma, and two sarcomas derived from four different inbred mouse strains. Anti-CD25 mAb (PC61) showed an effect in six of the eight tumors. Administration of anti-CD25 mAb (PC61) caused a reduction in the number of CD4+ CD25+ cells in the peripheral lymphoid tissues. The findings suggested that CD4+ CD25+ immunoregulatory cells were involved in the growth of those tumors. Kinetic analysis showed that the administration of anti-CD25 mAb (PC61) later than day 2 after tumor inoculation caused no tumor regression, irrespective of depletion of CD4+ CD25+ immunoregulatory cells. Two leukemias, on which the PC61-treatment had no effect, seemed to be incapable of eliciting effective rejection responses in the recipient mice because of low or no antigenicity.
免疫调节已被证明与某些小鼠肿瘤的渐进性生长有关。在本研究中,我们证明,单次体内给予剂量小于0.125 mg的抗CD25白细胞介素2受体α单克隆抗体(mAb;PC61)可使同基因小鼠体内渐进性生长的肿瘤消退。所使用的肿瘤包括五种白血病、一种骨髓瘤以及源自四种不同近交系小鼠的两种肉瘤。抗CD25 mAb(PC61)在八种肿瘤中的六种中显示出效果。给予抗CD25 mAb(PC61)导致外周淋巴组织中CD4 + CD25 +细胞数量减少。这些发现表明CD4 + CD25 +免疫调节细胞参与了这些肿瘤的生长。动力学分析表明,在肿瘤接种后第2天之后给予抗CD25 mAb(PC61)不会导致肿瘤消退,无论CD4 + CD25 +免疫调节细胞是否被清除。PC61治疗无效的两种白血病,由于抗原性低或无抗原性,似乎无法在受体小鼠中引发有效的排斥反应。