Spendlove I, Li L, Carmichael J, Durrant L G
Cancer Research Campaign Academic Unit of Clinical Oncology, University of Nottingham, City Hospital, United Kingdom.
Cancer Res. 1999 May 15;59(10):2282-6.
The 791Tgp72 antigen has been used successfully as a target for tumor imaging and T-cell immunotherapy. We have characterized this antigen using the monoclonal antibody 791T/36 as a 72/66 kDa doublet. NH2-terminal protein sequencing of the two bands revealed identity with the complement regulatory protein CD55. Antibodies recognizing different domains of CD55 were also shown to bind to the purified 791Tgp72, although sequence analysis of the cDNA cloned from 791T tumor cells showed 100% homology with CD55 and transfection of the cDNA into antigen-negative CHO cells resulted in binding of 791T/36. This identifies the tumor antigen 791Tgp72 as CD55. This protein protects cells from complement attack; however, it can also transduce signals in lymphocytes and is a ligand for CD97, expressed by activated T cells. These results suggest that CD55 plays a role in signaling between the innate and adaptive immune responses. It is therefore a very intriguing target, because absence of the molecule makes the tumor cells susceptible to complement, whereas protective overexpression results in the antigen being a target for T-cell immunotherapy.
791Tgp72抗原已成功用作肿瘤成像和T细胞免疫治疗的靶点。我们使用单克隆抗体791T/36将该抗原鉴定为72/66 kDa的双峰。对这两条带进行氨基末端蛋白质测序，结果显示与补体调节蛋白CD55相同。识别CD55不同结构域的抗体也显示与纯化的791Tgp72结合，尽管从791T肿瘤细胞克隆的cDNA的序列分析显示与CD55具有100%的同源性，并且将该cDNA转染到抗原阴性的CHO细胞中导致791T/36的结合。这表明肿瘤抗原791Tgp72就是CD55。这种蛋白可保护细胞免受补体攻击；然而，它也能在淋巴细胞中传导信号，并且是活化T细胞表达的CD97的配体。这些结果表明CD55在先天性免疫应答和适应性免疫应答之间的信号传导中发挥作用。因此，它是一个非常引人关注的靶点，因为该分子的缺失会使肿瘤细胞易受补体攻击，而保护性的过表达会使该抗原成为T细胞免疫治疗的靶点。
