乳癌疫苗鼠体实验获突破性发展
据美国《世界日报》报道,乳癌疫苗现在有突破性发展。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型乳癌分子增生的刺激免疫系统新疫苗,已在老鼠身上实验成功。瑞典的合作机构并已进行癌末病人临床试验。
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,并广获欧美各媒体报道。这个疫苗对现行hercepting治疗癌药已产生抗体,癌细胞重生的患者而言,是一个希望,可能预防HER-2型乳癌患者的HER-2癌分子再生。
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,乳癌患者中,罹HER-2型乳癌者约占三成。林维仁说,人体正常细胞中,HER-2蛋白质表现十分微量,但在许多肿瘤细胞中,尤其是乳癌细胞中,常常可以发现HER-2蛋白质过度表现。
她的研究是将脱氧核醣核酸(DNA)疫苗打入老鼠肌肉细胞,快速的唤醒免疫系统,使其辨识HER-2分子,并采取行动,让免疫系统产生大量抗体,对乳癌细胞中的HER-2 蛋白质发动攻击,而正常细胞因为HER-2蛋白质较少而躲过。
林维仁说,她的团队提供瑞典的合作机构,进行乳癌第四期病人的初步临床试验,到目前为止并无发生直接副作用。林维仁说,现在在动物体上实验的结果虽然很不错,但从实验到广泛使用,还有很长的路要走。林维仁强调,预防胜于治疗,鼓励大家多吃蔬果、多做运动,放松心情。
原始出处:
Cancer Research 68, 7502-7511, September 15, 2008. doi: 10.1158/0008-5472.CAN-08-1489
DNA Vaccination Controls Her-2+ Tumors that Are Refractory to Targeted Therapies
Paula J. Whittington, Marie P. Piechocki, Henry H. Heng, Jennifer B. Jacob, Richard F. Jones, Jessica B. Back, and Wei-Zen Wei
1 Department of Immunology and Microbiology, School of Medicine and 2 Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
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.
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