成纤维细胞介导的IL－4基因疗法对小鼠浆细胞瘤的治疗效果

Thetherapeuticeffectsoffibroblast┐mediatedIL┐4genetherapyonJ558Lplasmacytoma┐bearingmice

为观察白细胞介素４（ＩＬ－４）基因疗法对晚期浆细胞瘤的治疗作用，用成纤维细胞介导的ＩＬ－４基因疗法治疗小鼠Ｊ５５８Ｌ浆细胞瘤，并对其免疫学机制进行了初步探讨。对经治疗小鼠存活期的观察表明，该疗法对早期荷瘤小鼠（荷瘤３天以内）无明显治疗效果；而对晚期荷瘤小鼠（荷瘤１０天以上）则具有较明显的治疗效果；当与常规瘤苗联合应用时其疗效更加明显。对经治疗的荷瘤小鼠体内抗肿瘤免疫功能的检测表明，晚期荷瘤小鼠经ＩＬ－４基因治疗后第１２天，脾细胞ＮＫ活性及经诱导后的ＬＡＫ活性变化不明显，而经诱导的ＣＴＬ杀伤活性明显提高；当与常规瘤苗联合应用时ＣＴＬ杀伤活性的提高更为明显。结果显示，成纤维细胞介导的ＩＬ－４基因疗法主要通过增强ＣＴＬ杀伤活性而对晚期浆细胞瘤小鼠发挥治疗作用。

Toinvestigatethetherapeuticefectofinterleukin4(IL-4)onplasmacytoma,J558Lplas-macytoma-bearingmiceweretreatedwithfibroblast-mediatedIL-4genetherapyincombinationwithtu-morcelularvaccines(TCV).Afterinoculationoftumorcels,thetherapeuticefectwasnotsignificantwhenthegenetherapywasgiventhreedayslater,butwassignificantwhengiventendayslater.ThetherapeuticefectwasbetterwhenthegenetherapywasgivenincombinationwithTCV.ThecytotoxicityofCTLinducedfromthesplenocytesoftumor-bearingmicewasincreasedsignificantly,whiletheNKandLAKactivityremainedunchanged.TheresultsdemonstratedthattheadvancedplasmacytomacouldbetreatedefectivelybyIL-4genetherapythroughpotentinductionofCTL.