Niitsu Y, Kohgo Y, Watanabe N
Dept. of Internal Medicine (Section 4), Sapporo Medical College.
Gan To Kagaku Ryoho. 1990 Aug;17(8 Pt 1):1407-13.
TNF, IFN, LT and IL-1 are well-known biological response modifiers (BRM) with cytocidal activity. Whereas carcinostatic agents generally derive their cytocidal action from their direct mutual reaction with target molecules (e.g., DNA, RNA), the cytocidal action of BRM resides in the enzyme response which ensures upon their binding to receptors. Accordingly, concomitant use of these drug of differing mechanism of action has a rationale. Considering that a certain kind of counteracting protein is present in cancer cells which are refractory or resistant to such cytokines, combination therapy with carcinostatic agents with inhibitive activity against such protein is also justified. In the same context the effects of TIL and LAK activated by IL-2 could be enhanced if the immune system should be modulated by combined use of BRM and carcinostatic agents such as CY. This paper discusses the results obtained with BRM and carcinostatic agents in combination in animal models and clinical cases.
肿瘤坏死因子(TNF)、干扰素(IFN)、淋巴毒素(LT)和白细胞介素-1(IL-1)是众所周知的具有杀细胞活性的生物反应调节剂(BRM)。虽然抗癌剂的杀细胞作用通常源于它们与靶分子(如DNA、RNA)的直接相互反应,但BRM的杀细胞作用在于其与受体结合后所引发的酶反应。因此,同时使用这些作用机制不同的药物是有道理的。考虑到癌细胞中存在某种对这类细胞因子难治或耐药的抵消蛋白,联合使用对这类蛋白具有抑制活性的抗癌剂进行联合治疗也是合理的。在相同背景下,如果通过联合使用BRM和如环磷酰胺(CY)等抗癌剂来调节免疫系统,那么由白细胞介素-2激活的肿瘤浸润淋巴细胞(TIL)和淋巴因子激活的杀伤细胞(LAK)的效果可能会增强。本文讨论了在动物模型和临床病例中联合使用BRM和抗癌剂所获得的结果。