Saijo N, Ozaki A, Sakurai M, Ishihara J, Takahashi H, Sasaki Y, Hoshi A, Hamburger A W
Jpn J Cancer Res. 1986 May;77(5):487-93.
The immunosuppressive effect of a water-soluble nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), was evaluated in terms of the cytotoxicity of spleen lymphocytes, and the restoring effect of lymphokine-activated killer (LAK) cells and/or human recombinant interleukin-2 (rIL-2) on the cytotoxicities of spleen lymphocytes was examined in ACNU-treated C57BL/6 mice. In addition, we tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases. The administration of LAK cells and/or human rIL-2 restored the cytotoxicity of spleen lymphocytes against YAC-1 and syngeneic B-16 melanoma cells in ACNU-treated mice, and these treatments partially suppressed the increased numbers of artificial pulmonary metastases of B-16 melanoma cells in ACNU-treated mice. These results are extremely important in providing a rationale for the introduction of adoptive immunotherapy using LAK cells and rIL-2 in patients with advanced cancer who are being treated with anticancer agent(s).
一种水溶性亚硝基脲衍生物1-(4-氨基-2-甲基-5-嘧啶基)甲基-3-(2-氯乙基)-3-亚硝基脲(ACNU)的免疫抑制作用，通过脾淋巴细胞的细胞毒性进行评估，并在经ACNU处理的C57BL/6小鼠中检测淋巴因子激活的杀伤(LAK)细胞和/或人重组白细胞介素-2(rIL-2)对脾淋巴细胞细胞毒性的恢复作用。此外，我们测试了给予LAK细胞和/或rIL-2是否能减少经ACNU处理的小鼠肺转移瘤数量的增加。ACNU的最大有效剂量抑制了脾淋巴细胞的细胞毒性，ACNU预处理增强了人工肺转移的诱导。给予LAK细胞和/或人rIL-2可恢复经ACNU处理的小鼠脾淋巴细胞对YAC-1和同基因B-16黑色素瘤细胞的细胞毒性，并且这些处理部分抑制了经ACNU处理的小鼠中B-16黑色素瘤细胞人工肺转移瘤数量的增加。这些结果对于为正在接受抗癌药物治疗的晚期癌症患者引入使用LAK细胞和rIL-2的过继性免疫疗法提供理论依据极为重要。
