12月14日，美国科学家研制出一种能够攻击实验鼠体内癌细胞的疫苗，并且希望这项突破性成果未来能够帮助战胜人类的乳腺、大肠、卵巢和胰腺癌。相关论文"Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine发表在最新一期PNAS上。
虽然老鼠的试验成果往往不能直接在人体发挥治疗作用，但是因为这种疫苗的强度和独特作用方式，还是让研究人员充满希望。
研究者之一、乔治亚大学癌症中心化学教授布恩斯说：“该疫苗诱发了非常强的免疫反应，这会激活免疫系统所有三种杀灭癌细胞的方法，让肿瘤的大小平均减小了80%。”
研究人员说，这种疫苗通过培养免疫系统，去攻击表面带有MUC1蛋白质的癌细胞，发挥消灭肿瘤的作用。
医学人员已在超过70%最具侵犯性和最致命的癌细胞上发现了MUC1蛋白质，包括大部分的乳腺癌、胰腺癌、卵巢癌和多发性骨髓瘤。
研究合作者、亚利桑那州梅奥诊所的亨德勒教授说，“这是第一次开发出能够培养免疫系统按照蛋白质不同的糖结构来识别和杀死癌细胞的疫苗。”
在90%的“三阴性”(triple-negative)乳腺癌患者中，也有MUC1蛋白质超表达(overexpressed)问题。荷尔蒙疗法、比如他莫昔芬(Tamoxifen)，芳香化酶抑制剂(Aromatase inhibitors)或抗癌药物赫赛汀(Herceptin)对三阴性乳癌都没有反应。这类病人急需新的方法来治疗。
研究人员还说，这种新研发的疫苗可以跟化学疗法相结合，也可以作为高危人群的防癌措施。（生物谷Bioon.com）
doi:10.1073/pnas.1115166109
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PMID:
Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine
Lakshminarayanan, Vani; Thompson, Pamela; Wolfert, Margreet A.; Buskas, Therese; Bradley, Judy M.; Pathangey, Latha B.; Madsen, Cathy S.; Cohen, Peter A.; Gendler, Sandra J.; Boons, Geert-Jan
The mucin MUC1 is typically aberrantly glycosylated by epithelial cancer cells manifested by truncated O-linked saccharides. The resultant glycopeptide epitopes can bind cell surface major histocompatibility complex (MHC) molecules and are susceptible to recognition by cytotoxic T lymphocytes (CTLs), whereas aberrantly glycosylated MUC1 protein on the tumor cell surface can be bound by antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Efforts to elicit CTLs and IgG antibodies against cancer-expressed MUC1 have not been successful when nonglycosylated MUC1 sequences were used for vaccination, probably due to conformational dissimilarities. Immunizations with densely glycosylated MUC1 peptides have also been ineffective due to impaired susceptibility to antigen processing. Given the challenges to immuno-target tumor-associated MUC1, we have identified the minimum requirements to consistently induce CTLs and ADCC-mediating antibodies specific for the tumor form of MUC1 resulting in a therapeutic response in a mouse model of mammary cancer. The vaccine is composed of the immunoadjuvant Pam3CysSK4, a peptide Thelper epitope and an aberrantly glycosylated MUC1 peptide. Covalent linkage of the three components was essential for maximum efficacy. The vaccine produced CTLs, which recognized both glycosylated and nonglycosylated peptides, whereas a similar nonglycosylated vaccine gave CTLs which recognized only nonglycosylated peptide. Antibodies elicited by the glycosylated tripartite vaccine were significantly more lytic compared with the unglycosylated control. As a result, immunization with the glycosylated tripartite vaccine was superior in tumor prevention. Besides its own aptness as a clinical target, these studies of MUC1 are likely predictive of a covalent linking strategy applicable to many additional tumor-associated antigens.
