Antibody Engineering, Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
J Immunol Methods. 2011 Aug 31;371(1-2):70-80. doi: 10.1016/j.jim.2011.06.017. Epub 2011 Jun 30.
Carcinoembryonic antigen related cell adhesion molecule (CEACAM) 6 is over-expressed in different types of cancer cells. In addition, it has also been implicated in some infectious diseases. Targeting this molecule by an antibody might have applications in diverse tumor models. Single domain antibody (sdAb) is becoming very useful format in antibody engineering as potential tools for treating acute and chronic disease conditions such as cancer for both diagnostic as well as therapeutic application. Generally, sdAbs with good affinity are isolated from an immune library. Discovery of a new target antigen would require a new immunization with purified antigen which is not always easy. In this study, we have isolated, by phage display, an sdAb against CEACAM6 with an affinity of 5 nM from a llama immunized with cancer cells. The antibody has good biophysical properties, and it binds to the cells expressing the target antigen. Furthermore, it reduces cancer cells proliferation in vitro and shows an excellent tumor targeting in vivo. This sdAb could be useful in diagnosis as well as therapy of CEACAM6 expressing tumors. Finally, we envisage it would be feasible to isolate good sdAbs against other interesting tumor associated antigens from this library. Therefore, this immunization method could be a general strategy for isolating sdAbs against any surface antigen without immunizing the animal with the antigen of interest each time.
癌胚抗原相关细胞黏附分子 6（CEACAM）在不同类型的癌细胞中过度表达。此外，它还与一些传染病有关。通过抗体靶向该分子可能在多种肿瘤模型中具有应用。单域抗体（sdAb）在抗体工程中作为治疗癌症等急性和慢性疾病的潜在工具变得非常有用，可用于诊断和治疗。通常，从免疫文库中分离出具有良好亲和力的 sdAb。发现新的靶抗原需要用纯化抗原进行新的免疫，这并不总是容易的。在这项研究中，我们从用癌细胞免疫的骆驼中通过噬菌体展示分离出了一种针对 CEACAM6 的 sdAb，其亲和力为 5 nM。该抗体具有良好的物理特性，可与表达靶抗原的细胞结合。此外，它还能抑制体外癌细胞的增殖，并在体内显示出优异的肿瘤靶向性。该 sdAb 可用于诊断和治疗表达 CEACAM6 的肿瘤。最后，我们设想可以从该文库中分离出针对其他有趣的肿瘤相关抗原的良好 sdAb。因此，这种免疫方法可以作为一种通用策略，用于分离针对任何表面抗原的 sdAb，而无需每次都用感兴趣的抗原免疫动物。
