随着FDA近期批准了首支治疗性癌症疫苗，癌症研究进入了疫苗研发的新纪元，近期来自梅奥诊所医学院，佐治亚大学的研究人员发表了题为 “Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine”的文章，首次开发出利用免疫系统按照蛋白不同的糖结构，识别和杀死癌细胞的疫苗，这种疫苗能对抗70%的癌症，是目前所得到的最广泛的癌症预防疫苗，相关成果公布在PNAS杂志上。
文章的通讯作者是佐治亚大学癌症中心的Geert-Jan Boons教授，以及梅奥诊所的Sandra J. Gendler教授，Boons教授表示，“这种疫苗引起了一个高强度的免疫反应，能够激活免疫系统3大要素，缩减肿瘤的大小平均80%左右”。
随着FDA近期批准首支治疗性癌症疫苗——用于治疗前列腺癌的Provenge，以及预防性疫苗在临床实验中的好消息，代表着我们正在进入癌症疫苗研发的新纪元。这项最新的疫苗成果证明能用于小鼠的乳腺癌，前列腺癌、胰腺癌、肠癌和卵巢癌，虽然小鼠试验还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。
这种疫苗的不同之处在于其利用的是免疫系统对抗肿瘤——一般疫苗主要是针对癌细胞，这种疫苗通过培养免疫系统，攻击表面带有Muc1蛋白的癌细胞，发挥消灭肿瘤的作用。之前的研究表明MUC1蛋白在超过70%最具侵略性和致命性的癌症上都被发现过，包括大部分的乳腺癌，胰腺癌，卵巢癌和多发性骨髓瘤。
这种特性使得这种疫苗大大优于癌症病人目前常常使用的其他药物，比如当前市场上的“万灵药”赫赛汀，因为目前市售的抗癌药或多或少都会伤害健康的体细胞，有些药物不仅消灭不了癌细胞还会伤害破坏健康体细胞。
通过靶定Muc1蛋白，研究人员就靶定了癌细胞特殊的糖结构，从而激活免疫系统，一旦发现癌细胞，大量抗体就会包围它们，并最终将其消灭，这种利用免疫系统识别出癌细胞的方法，能有效的分别癌细胞与正常细胞，定位后吞噬，更有效，特异性也更强。
从结构上来说，这种疫苗也具有独特性，它是由三部分组成，能分别激活免疫系统的三个组成部分，研究人员发现Muc1蛋白表达的乳腺癌患者中会出现所谓的三阴性”(triple-negative)，也有MUC1蛋白质超表达(overexpressed)问题，一些激素疗法，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)对三阴性乳癌都无效，而这种疫苗也许能通过激活免疫系统的多个部分，有效的控制此类病患病情。
目前研究人员正在积极进行人体实验，希望能在后年获得人体试验的新成果，并于2020年将该疫苗推出市场。
原文摘要：
Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine
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.
