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Biochim Biophys Acta:母乳也成抗癌利器?新研究开启乳铁蛋白“杀手”模式

2017-04-14 佚名 转化医学网

在一项由奥地利科学基金(FWF)资助的项目中,奥地利格拉茨大学的科学家们对母乳中的某种宿主防御肽进行了改造,使其能够特异性识别并攻击癌细胞。这种存在于多种哺乳动物母乳中的活性大分子可以诱导细胞凋亡,具有潜在的癌症治疗价值。

在一项由奥地利科学基金(FWF)资助的项目中,奥地利格拉茨大学的科学家们对母乳中的某种宿主防御肽进行了改造,使其能够特异性识别并攻击癌细胞。这种存在于多种哺乳动物母乳中的活性大分子可以诱导细胞凋亡,具有潜在的癌症治疗价值。

目前,科学家和临床医生已经能够对多种癌症进行化疗治疗并取得良好疗效。可是包括皮肤癌和脑癌(胶质母细胞瘤)等转移瘤的治疗仍然是一个难题,但即便是最难治愈的肿瘤也有其致命弱点。与健康细胞不同,包膜癌细胞外侧存在大量脂质磷脂酰丝氨酸(PS)分子,而后者在某些情况下正可作为癌症治疗的靶标。在奥地利科学基金会(FWF)的支持下,格拉茨大学分子生物科学系研究团队开发了一种新武器,针对PS这一癌细胞的弱点选择性地对其进行攻击。

母乳多肽与靶向药物

在上述FWF项目中,主要参与研究的Dagmar Zweytick团队已经确定,PS癌症标志物可以作为抗肿瘤药物的合适靶标,PS可以在各种类型甚至是转移瘤的细胞膜上检测到。

后续项目中,该团队将存在于母乳中的人类抗原肽重编成为靶向PS抗体。带正电荷的人类抗原肽会选择性地定位暴露于癌细胞表面负电PS,停靠于其上并在数小时内诱导细胞死亡

对癌细胞的杀伤专一性

“靶向肽设计过程中的最大挑战可谓是寻找最为适当的毒性和特异性平衡,如果多肽太过活跃,它们就会攻击健康的细胞。在对照试验中,我们确保了多肽只能定位于癌细胞并远离正常细胞。”研究对应文章的主要作者Dagmar Zweytick博士表示。

自2002年以来,生物物理学家一直在研究乳铁蛋白。这种蛋白质的前体分子大量存在于母乳中,在为婴儿提供养分的同时还可以帮助他们建立强大的抗微生物防御系统。作为先天免疫系统的一部分,乳铁蛋白是身体对包括真菌和细菌细胞在内负电外源细胞的第一个防御机制。同时,特殊的乳铁蛋白也可以对癌细胞等突变细胞产生防御作用。

2012年7月至2016年6月期间,这一由FWF资助的团队将时间与精力集中在了开发发夹状活性肽单元。通过计算机模拟,该团队开始设计满足癌细胞特异性的多肽变体。研究人员筛选出大约十五种物质变体并在癌细胞系上进行了“体外”测试。

肿瘤特异抗体的筛选

通过与格拉茨医科大学的合作与大量测试,研究人员最终将目光集中在了2种多肽变体上。研究人员对经过这种多肽治疗和未经治疗的肿瘤小鼠进行了对比,发现与未经治疗的肿瘤小鼠相比得到上述多肽变体治疗的小鼠发现明显病情好转甚至肿瘤组织的完全消失。

目前,这种具有抗肿瘤作用的活性肽变体已经在欧盟和美国申请专利。Dagmar Zweytick博士则正在与一家制药公司开展合作,在由奥地利研究促进局(FFG)的资助下准备临床前研究。

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    2017-08-30 windight
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    2017-05-17 sunylz
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    2017-04-16 仁医06
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    2017-04-15 卡圣

    谢谢分享,学习了

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