华裔女科学家乳腺癌研究取得重大突破

　　

据报道，乳腺癌疫苗研究取得突破性进展。美国华裔科学家林维仁(Weizen  Wei)领导的团队，研究出可预防HER-2型乳腺癌分子增生新疫苗，已在小鼠模型上进行疫苗效果测定，效果良好。瑞典的合作机构已开始进行癌症末期病人临床试验。  

美国癌症研究学会的《癌症研究》期刊9月15日刊出林维仁团队的研究报告。这一新的疫苗为现行hercepting耐药的癌症患者带来希望。对hercepting耐药的患者经过治疗后容易复发癌症。新的疫苗可预防HER-2型乳癌患者治愈后复发。  

林维仁是底特律韦恩州立大学(Wayne  State  University)医学院卡门诺斯(Karmanos)癌症研究所的免疫及微生物系教授。她15日受访时指出，乳腺癌患者中，罹HER-2型乳癌者约占30%。人体正常细胞中，HER-2蛋白质表达十分微量，但在许多肿瘤细胞中，尤其是乳腺癌细胞中，常常可以发现HER-2蛋白质过度表达。  

 

她研究的新型疫苗是DNA苗，将疫苗注入小鼠的肌肉细胞，可快速激活免疫系统，使免疫细胞识别HER-2分子，B细胞产生大量抗体，对表达HER-2  蛋白的癌细胞发起攻击，而正常细胞因为HER-2蛋白质较少而不被抗体识别。  

林维仁说，她的团队与瑞典的研究机构合作，进行乳腺癌第四期病人的初步临床试验，到目前为止并没发现有明显的毒副作用。林维仁说，现在在动物体上实验的结果虽然很不错，但从实验到临床应用，还有很长的路要走，还需要更细致的研究验证。林维仁强调，预防胜于治疗，鼓励民众多吃蔬果、多做运动，放松心情。

原文摘要：DNA Vaccination Controls Her-2⁺ Tumors that Are Refractory to Targeted Therapies

 

【Abstract】

Her-2/neu+ tumor cells refractory to antibody or receptor tyrosine kinase inhibitors are emerging in treated patients. To investigate if drug resistant tumors can be controlled by active vaccination, gefitinib and antibody sensitivity of four neu+ BALB/c mouse mammary tumor lines were compared. Significant differences in cell proliferation and Akt phosphorylation were observed. Treatment-induced drug resistance was associated with increased chromosomal aberrations as shown by spectral karyotyping analysis, suggesting changes beyond neu signaling pathways. When mice were immunized with pneuTM encoding the extracellular and transmembrane domains of neu, antibody and T-cell responses were induced, and both drug-sensitive and drug-resistant tumor cells were rejected. In T-cell–depleted mice, drug-sensitive tumors were still rejected by vaccination, but drug-refractory tumors survived in some mice, indicating their resistance to anti-neu antibodies. To further test if T cells alone can mediate tumor rejection, mice were immunized with pcytneu encoding full-length cytoplasmic neu that is rapidly degraded by the proteasome to activate CD8 T cells without inducing antibody response. All test tumors were rejected in pcytneu-immunized mice, regardless of their sensitivity to gefitinib or antibody. Therefore, cytotoxic T lymphocytes activated by the complete repertoire of neu epitopes were effective against all test tumors. These results warrant Her-2 vaccination whether tumor cells are sensitive or resistant to Her-2–targeted drugs or antibody therapy. [Cancer Res 2008;68(18):7502–11]

（生物通 张欢）