瘤体内注射脂质体包裹的IL－2基因的抗肿瘤作用及其局部免疫机理分析

ANTITUMOR EFFECTS OF DIRECT IL-2 GENE TRANSFER INTOTUMOR BY LIPOSOME AND ITS INDUCTION OF LOCAL IM-MUNE RESPONSE

脂质体可以介导体内的细胞因子基因治疗。将脂质体包裹的ＩＬ－２基因直接注射到小鼠黑色素瘤（Ｂ１６－Ｆ１０）瘤体内，结果发现，肿瘤的生长明显受到抑制，部分小鼠的瘤体完全消退，存活期明显延长；从瘤体中分离的肿瘤细胞经Ｇ４１８筛选后产生阳性克隆，其上清中分泌有ＩＬ－２；肿瘤局部浸润性淋巴细胞（ＴＩＬ）具有较高的杀伤活性，揭示瘤体内注射脂质体包裹的ＩＬ－２基因后，可增强肿瘤细胞的免疫原性，激活瘤体局部的抗肿瘤免疫功能。结果表明瘤体内注射脂质体包裹的ＩＬ－２基因具有良好的抗肿瘤效果。

Liposome can mediate in vivo cytokine gene therapy. IL-2 DNA-lipostome complexes wasinjected directly into melanoma in vivo. After the treatment,the tumor growth was suppresseddrarnatically and complete regression of tumor was observed in some lnice. The survival time oftumor-bearing mice was significantly( P <0. 01)longer than that of the control; Meanwhile ,tu-mor cells seperated from the treated mice were confirmed to secrete IL-2 after in vitro G418 re-sistant selection. The tumor infiltrating lymphocyte exhibited more potent cytotoxicity to B16melanoma cells. Those results demonstrated that direct intratumoral injection of IL-2 DNA-lipo-some complexes could enhance tumor immunogenicity and activate local antitumor immunity oftumor site, indicating that direct IL-2 gene transfer into tumor by liposome is a potential ap-proach for cancer treatment.