8-1A, a human monoclonal antibody that reacts with intact human chorionic gonadotropin.

Abstract The incidence of choriocarcinomahas decreased over time and therapeutic results have improved about 90% complete remission in patients without extensive metastasis. However, some choriocarcinomasmetastasize to other organs and show resistance to chemotherapy, having a poor prognosis despite multidisciplinary treatment. Better methods of early diagnosis for recurrence or micrometastasis, and treatment against cases with intractable gestational trophoblastic neoplasia(GTN) are needed to improve the prognosis. Human chorionic gonadotropin(hCG) is a glycoprotein hormone composed of two dissimilar subunits and a tumor marker to make a diagnosis and monitor therapeutic effect in GTN. Even when hCG levels in the serum become too low to measure with the hCG β-CTP system which is the most sensitive assay, there are estimated to be approximately 10,000 trophoblastic cellsin the body. Residual trophoblast cellsmay cause symptoms such as bleeding or undergo malignant transformation to choriocarcinoma. Since most monoclonal antibodiesdeveloped so far are murine, administration creates human anti-mouse antibodies, resulting in clinical failure. More recent mouse/human chimeric antibodiesor humanized antibodiesstill possess substantial immunogenicity that makes repeated administration difficult. In the present study, KM mice that can produce completely human monoclonal antibodieswere used to prepare hCG-specific human monoclonal antibody. This yielded 8-1A, a human monoclonal antibodycapable of reacting with intact hCG. In the future, new diagnostic techniques and treatments for chorionic diseases may be developed using this kind of human monoclonal antibody.