Linardakis Emmanouela, Bateman Andrew, Phan Vy, Ahmed Atique, Gough Michael, Olivier Kenneth, Kennedy Rick, Errington Fiona, Harrington Kevin J, Melcher Alan, Vile Richard
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Res. 2002 Oct 1;62(19):5495-504.
We have investigated how to make K1735 cells, a poor allogeneic melanoma vaccine, more effective for protection against B16 in vivo. To promote antigen release in an immunologically effective manner, tumor cells were transfected with a viral fusogenic membrane glycoprotein (vesicular stomatitis virus G glycoprotein), which kills cells through the formation, and degeneration, of large multinucleated syncytia. Vaccines consisting of a 1:1 mix of fusing allogeneic and autologous cells led to dramatic increases in survival of mice in both prophylactic and therapy models, dependent upon T cells, the mechanism of tumor-tumor cell fusion, and the nature of the fusion partner. Syncytia activate macrophages and fusogenic membrane glycoprotein-mediated cell killing very efficiently promotes cross-priming of immature dendritic cells with a model tumor antigen. Our data suggest that the unique manner in which syncytia develop and die provides a highly effective pathway for tumor antigen release and presentation to the immune system and offers a novel mechanism by which cancer cell vaccines may be prepared for clinical use.
我们研究了如何使K1735细胞（一种效果不佳的同种异体黑色素瘤疫苗）在体内对抵御B16更有效。为了以免疫有效的方式促进抗原释放，用一种病毒融合膜糖蛋白（水泡性口炎病毒G糖蛋白）转染肿瘤细胞，该糖蛋白通过形成和退化大的多核合胞体来杀死细胞。由融合的同种异体和自体细胞按1:1混合组成的疫苗，在预防性和治疗性模型中均使小鼠存活率显著提高，这取决于T细胞、肿瘤 - 肿瘤细胞融合机制以及融合伙伴的性质。合胞体可非常有效地激活巨噬细胞，并且融合膜糖蛋白介导的细胞杀伤极大地促进了未成熟树突状细胞对模型肿瘤抗原的交叉呈递。我们的数据表明，合胞体形成和死亡的独特方式为肿瘤抗原释放并呈递给免疫系统提供了一条高效途径，并为制备可用于临床的癌细胞疫苗提供了一种新机制。
