Watanabe Y, Uchida E, Higuchi M, Imai Y, Osawa T
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
J Biol Response Mod. 1987 Oct;6(5):556-68.
We prepared large unilamellar vesicles containing the cell-free culture supernatant of a human T cell hybridoma rich in macrophage activating factor (MAF) and bearing monoclonal antibodies against human melanoma A375 tumor cells; their antitumor activity against A375 cells was examined in vitro and in vivo. Both MAF-immunoliposomes (bearing antibodies) and MAF liposomes (not bearing antibodies) showed macrophage-mediated cytotoxicity in vitro at a high E/T ratio (about 40). But at a low E/T ratio (about 15), only MAF-immunoliposomes showed tumoricidal activity, their activity being more than ten thousand-fold stronger compared with a soluble MAF preparation (MAF solution). MAF-immunoliposomes not only showed tumor neutralization mediated by macrophages in vivo when a mixture of tumor cells, macrophages, and MAF-immunoliposomes was locally injected, but also showed significant inhibition of tumor growth on repeated i.v. systemic administration of them. On the other hand, other samples (MAF-liposomes without the antibody, a MAF solution, and immunoliposomes without MAF) were not significantly effective against tumor growth. These results may constitute evidence that the delivery of lymphokines to the tumor sites is important or even critical when an attempt is made to treat cancer with lymphokines with the expectation of the potentiation of the host's immune system.
我们制备了大单层囊泡，其包含富含巨噬细胞活化因子（MAF）且携带抗人黑色素瘤A375肿瘤细胞单克隆抗体的人T细胞杂交瘤的无细胞培养上清液；在体外和体内检测了它们对A375细胞的抗肿瘤活性。MAF免疫脂质体（携带抗体）和MAF脂质体（不携带抗体）在高E/T比（约40）时均在体外显示出巨噬细胞介导的细胞毒性。但在低E/T比（约15）时，只有MAF免疫脂质体显示出杀肿瘤活性，其活性比可溶性MAF制剂（MAF溶液）强一万多倍。当局部注射肿瘤细胞、巨噬细胞和MAF免疫脂质体的混合物时，MAF免疫脂质体不仅在体内显示出由巨噬细胞介导的肿瘤中和作用，而且在重复静脉全身给药时也显示出对肿瘤生长的显著抑制。另一方面，其他样品（不含抗体的MAF脂质体、MAF溶液和不含MAF的免疫脂质体）对肿瘤生长没有显著效果。这些结果可能证明，当试图用淋巴因子治疗癌症以期增强宿主免疫系统时，将淋巴因子递送至肿瘤部位很重要甚至至关重要。
