英國研究人員在新一期美國《臨床檢查雜志》上報告說,，他們發(fā)現(xiàn)抗體可不借助人體免疫系統(tǒng)而直接殺死癌細(xì)胞,，這一成果將有助開發(fā)出治療癌癥的新方法,。
抗體可用于治療癌癥,。其基本原理是,，當(dāng)抗體與癌細(xì)胞結(jié)合后，會使癌細(xì)胞更容易被人體免疫系統(tǒng)識別,，從而引導(dǎo)免疫系統(tǒng)來殺死癌細(xì)胞,。
英國南安普頓大學(xué)7月21日發(fā)布新聞公報說，該校和曼徹斯特大學(xué)等機(jī)構(gòu)的聯(lián)合研究小組發(fā)現(xiàn),，一些抗體還能繞開免疫系統(tǒng)直接殺死癌細(xì)胞,。這些抗體與癌細(xì)胞結(jié)合后，會導(dǎo)致癌細(xì)胞中的溶酶體脹裂并釋放出有毒物質(zhì),，最終使癌細(xì)胞死亡,。
研究人員說，這一發(fā)現(xiàn)有助于開發(fā)可高效殺滅癌細(xì)胞的新方法,，用于治療那些傳統(tǒng)化學(xué)療法無法醫(yī)治的癌癥,。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Clin. Invest. doi:10.1172/JCI37884.
Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells
Andrei Ivanov1, Stephen A. Beers2, Claire A. Walshe2, Jamie Honeychurch1, Waleed Alduaij1, Kerry L. Cox2, Kathleen N. Potter2, Stephen Murray1, Claude H.T. Chan2, Tetyana Klymenko1, Jekaterina Erenpreisa3, Martin J. Glennie2, Tim M. Illidge1 and Mark S. Cragg2
1CRUK Paterson Institute for Cancer Research, School of Cancer and Imaging Sciences, School of Medicine, University of Manchester, Manchester, United Kingdom.
2Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton, United Kingdom.
3Biomedical Research and Study Centre, Riga, Latvia.
mAbs are becoming increasingly utilized in the treatment of lymphoid disorders. Although Fc-FcγR interactions are thought to account for much of their therapeutic effect, this does not explain why certain mAb specificities are more potent than others. An additional effector mechanism underlying the action of some mAbs is the direct induction of cell death. Previously, we demonstrated that certain CD20-specific mAbs (which we termed type II mAbs) evoke a nonapoptotic mode of cell death that appears to be linked with the induction of homotypic adhesion. Here, we reveal that peripheral relocalization of actin is critical for the adhesion and cell death induced by both the type II CD20-specific mAb tositumomab and an HLA-DR–specific mAb in both human lymphoma cell lines and primary chronic lymphocytic leukemia cells. The cell death elicited was rapid, nonapoptotic, nonautophagic, and dependent on the integrity of plasma membrane cholesterol and activation of the V-type ATPase. This cytoplasmic cell death involved lysosomes, which swelled and then dispersed their contents, including cathepsin B, into the cytoplasm and surrounding environment. The resulting loss of plasma membrane integrity occurred independently of caspases and was not controlled by Bcl-2. These experiments provide what we believe to be new insights into the mechanisms by which 2 clinically relevant mAbs elicit cell death and show that this homotypic adhesion–related cell death occurs through a lysosome-dependent pathway.
