摘要
目的探讨HER-2/neu胞外配体第2结构域(RLD2)作为肿瘤疫苗在抗乳腺癌免疫中的作用。方法纯化出目的蛋白HER-2/neu胞外配体第2结构域,同时选取10例经免疫组化证实为HER-2/neu阳性的乳腺癌,用RLD2分别负荷这10名患者外周血来源的树突状细胞(DC),再诱导抗原特异的细胞因子诱导的杀伤细胞(CIK),将DC与C IK共培养,研究其对HER-2/neu阳性、阴性肿瘤细胞株和自体乳腺癌细胞杀伤活性的作用。结果RLD2诱导的特异性CIK对HER-2/neu阳性肿瘤细胞SKBR-3以及自体乳腺癌细胞的杀伤活性,较之单独CIK组更高,差异有统计学意义(P<0.01);RLD2诱导的特异性C IK对HER-2/neu阴性细胞MDA-435的杀伤活性与单独C IK组之间差异无统计学意义(P>0.05)。结论负载RLD2的DCs诱导的C IK对HER-2/neu阳性肿瘤细胞以及自体乳腺癌肿瘤有特异性杀伤能力,RLD2可能成为新型肿瘤疫苗应用于临床乳腺癌免疫治疗。
Objective To investigate the role of L2 domain of HER-2/neu （ ErbB2 ） ectodomain （ RLD2 ） as vaccine in the course of anti-breast tumor response. Methods RLD2 was expressed in E. coli and purified. Peripheral blood mononuclear cells （ PBMC ） from 10 patients with HER-2/neu positive breast cancer were cultured with granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-4 （ IL-4 ） to produce DC. T lymphocytes from PBMC were cultured with interferon-γ（IFN-γ） , IL-2, CD3-moAb, and IL-1αto prepare CIK. The killing activity of CIK on autologous breast cancer cells, MDA-435 and SKBR-3 was investigated after CIK was incubated with RLD2-pulsed DC. Resuits The killing activity of CIK on autologous breast cancer cells and SKBR-3 was improved remarkably after CIK was incubated with RLD2-pulsed DC （ P 〈 0.05 ）. There was no significant difference in the killing activity of MDA-435 between CIK and CIK incubated with RLD2-pulsed DC （ P 〉 0.05 ）. Conclusion RLD2-pulsed DC in combination with CIK shows short-term efficacy on autologous breast cancer cells and SKBR-3 through inducing specific antitumor immunity, RLD2 may be selected as new tumor vaccine to induce anti-ErbB2 response.
出处
《中国输血杂志》
CAS
CSCD
2008年第4期250-254,共5页
Chinese Journal of Blood Transfusion
基金
国家自然科学基金资助项目(30070858)
四川省卫生厅科学研究项目(050288)
