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上皮膜蛋白2多肽疫苗在鼠乳腺癌中的免疫防治效果研究

, PP. 2338-2342

Keywords: 乳腺癌,组织芯片,生物标志物,疫苗

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Abstract:

目的研究上皮膜蛋白2(epithelialmembraneprotein2,EMP2)在多种人类肿瘤中的蛋白表达谱,并在小鼠乳腺癌模型中研究EMP2多肽疫苗的预防及治疗效果。方法采用大样本组织芯片检测人体常见20种肿瘤中,EMP2在正常组织与相对应的肿瘤组织的表达。体外化学合成EMP2多肽,并与KLH蛋白偶联。于小鼠接瘤前后免疫Balb/c小鼠,ELISA法检测免疫后小鼠抗EMP2抗体的血清效价。建立4T1细胞荷瘤小鼠预防及治疗模型,随机分为生理盐水组、单纯KLH组、单纯佐剂组、KLH-EMP2多肽组,每组各10只。观察KLH-EMP2多肽疫苗对乳腺癌模型的成瘤率、肿瘤生长情况、体重及生存期的影响。结果与相应正常组织比较,EMP2在乳腺癌、子宫内膜癌、卵巢癌、宫颈癌、膀胱癌、甲状腺癌等肿瘤中明显高表达。而在胰腺癌、前列腺癌及脑部肿瘤中呈低表达或阴性表达。KLH-EMP2多肽免疫小鼠后,构建小鼠乳腺癌4T1荷瘤模型,对照组成瘤率为100%,佐剂组及单纯KLH组成瘤率分别为100%,100%,KLH-EMP2多肽组成瘤率为70%。较之对照组、佐剂组及单纯KLH组,KLH-EMP2多肽组可明显抑制4T1肿瘤生长(P=0.009)。同时,延长荷瘤小鼠生存时间(P=0.001),同时,免疫对小鼠的体重无明显变化(P=0.58)。在4T1肿瘤治疗模型中,KLH-EMP2多肽治疗可明显抑制4T1肿瘤生长(P=0.001)和大小(P=0.006)。同时,延长4T1荷瘤小鼠生存期(P=0.03)。结论EMP2在乳腺癌中呈高表达,EMP2多肽疫苗具有明显的乳腺癌预防及治疗作用。

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