英国研究人员在新一期美国《临床检查杂志》上报告说，他们发现抗体可不借助人体免疫系统而直接杀死癌细胞，这一成果将有助开发出治疗癌症的新方法。
抗体可用于治疗癌症。其基本原理是，当抗体与癌细胞结合后，会使癌细胞更容易被人体免疫系统识别，从而引导免疫系统来杀死癌细胞。
英国南安普顿大学7月21日发布新闻公报说，该校和曼彻斯特大学等机构的联合研究小组发现，一些抗体还能绕开免疫系统直接杀死癌细胞。这些抗体与癌细胞结合后，会导致癌细胞中的溶酶体胀裂并释放出有毒物质，最终使癌细胞死亡。
研究人员说，这一发现有助于开发可高效杀灭癌细胞的新方法，用于治疗那些传统化学疗法无法医治的癌症。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
