Wang Y, Qian X J, Hadley H R, Lau B H
Department of Urology, School of Medicine, Loma Linda University, CA 92350.
Mol Biother. 1992 Sep;4(3):143-6.
The success of adoptive immunotherapy using recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in several cancers has been hampered by severe toxicity associated with high doses of rIL-2. Methods that reduce the dosage of rIL-2 without loss of clinical efficacy are needed. In this study we determined the in vitro effect of a phytochemical immune modulator, Astragalus membranaceus (AM), and two fractions isolated by high-performance liquid chromatography on the cytotoxicity of rIL-2-generated LAK cells against a murine renal cell carcinoma. Our results indicated a 10-fold potentiation of rIL-2-generated LAK cell cytotoxicity manifested by tumor cell lysis of 88% in the group with 100 U/ml of rIL-2 plus AM versus 86% in the group with 1,000 U/ml of rIL-2 alone. Potentiation was obtained with the purified fractions as well. A significantly reduced number of LAK cells was required to achieve the tumor cytotoxicity after LAK cell generation with rIL-2 plus the phytochemicals as compared with rIL-2 alone. Our data indicate that AM is an effective immune modulator, capable of potentiating in vitro the antitumor activity of rIL-2-generated LAK cells.
使用重组白细胞介素-2(rIL-2)和淋巴因子激活的杀伤细胞(LAK)进行的过继性免疫疗法在多种癌症治疗中的成功,受到高剂量rIL-2相关的严重毒性的阻碍。需要在不损失临床疗效的情况下降低rIL-2剂量的方法。在本研究中,我们测定了一种植物化学免疫调节剂黄芪(AM)以及通过高效液相色谱法分离得到的两个组分对rIL-2诱导产生的LAK细胞针对小鼠肾细胞癌的细胞毒性的体外作用。我们的结果表明,rIL-2诱导产生的LAK细胞的细胞毒性增强了10倍,在含有100 U/ml rIL-2加AM的组中,肿瘤细胞裂解率为88%,而在仅含有1000 U/ml rIL-2的组中为86%。纯化的组分也能产生增强作用。与单独使用rIL-2相比,在用rIL-2加植物化学物质产生LAK细胞后,达到肿瘤细胞毒性所需的LAK细胞数量显著减少。我们的数据表明,AM是一种有效的免疫调节剂,能够在体外增强rIL-2诱导产生的LAK细胞的抗肿瘤活性。