12月14日,，美國(guó)科學(xué)家研制出一種能夠攻擊實(shí)驗(yàn)鼠體內(nèi)癌細(xì)胞的疫苗，并且希望這項(xiàng)突破性成果未來(lái)能夠幫助戰(zhàn)勝人類(lèi)的乳腺,、大腸,、卵巢和胰腺癌。相關(guān)論文"Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine發(fā)表在最新一期PNAS上,。
雖然老鼠的試驗(yàn)成果往往不能直接在人體發(fā)揮治療作用,，但是因?yàn)檫@種疫苗的強(qiáng)度和獨(dú)特作用方式,，還是讓研究人員充滿(mǎn)希望,。
研究者之一、喬治亞大學(xué)癌癥中心化學(xué)教授布恩斯說(shuō)：“該疫苗誘發(fā)了非常強(qiáng)的免疫反應(yīng),，這會(huì)激活免疫系統(tǒng)所有三種殺滅癌細(xì)胞的方法,，讓腫瘤的大小平均減小了80%,。”
研究人員說(shuō)，這種疫苗通過(guò)培養(yǎng)免疫系統(tǒng),，去攻擊表面帶有MUC1蛋白質(zhì)的癌細(xì)胞,，發(fā)揮消滅腫瘤的作用。
醫(yī)學(xué)人員已在超過(guò)70%最具侵犯性和最致命的癌細(xì)胞上發(fā)現(xiàn)了MUC1蛋白質(zhì),，包括大部分的乳腺癌,、胰腺癌、卵巢癌和多發(fā)性骨髓瘤,。
研究合作者,、亞利桑那州梅奧診所的亨德勒教授說(shuō)，“這是第一次開(kāi)發(fā)出能夠培養(yǎng)免疫系統(tǒng)按照蛋白質(zhì)不同的糖結(jié)構(gòu)來(lái)識(shí)別和殺死癌細(xì)胞的疫苗,。”
在90%的“三陰性”(triple-negative)乳腺癌患者中,，也有MUC1蛋白質(zhì)超表達(dá)(overexpressed)問(wèn)題。荷爾蒙療法,、比如他莫昔芬(Tamoxifen),，芳香化酶抑制劑(Aromatase inhibitors)或抗癌藥物赫賽汀(Herceptin)對(duì)三陰性乳癌都沒(méi)有反應(yīng)。這類(lèi)病人急需新的方法來(lái)治療,。
研究人員還說(shuō),，這種新研發(fā)的疫苗可以跟化學(xué)療法相結(jié)合，也可以作為高危人群的防癌措施,。（生物谷Bioon.com）
doi:10.1073/pnas.1115166109
PMC:
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.
