8-1A, a human monoclonal antibody that reacts with intact human chorionic gonadotropin.
The incidence of choriocarcinoma has decreased over time and therapeutic results have improved about 90% complete remission in patients without extensive metastasis. However, some choriocarcinomas metastasize 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 beta-CTP system which is the most sensitive assay, there are estimated to be approximately 10,000 trophoblastic cells in the body. Residual trophoblast cells may cause symptoms such as bleeding or undergo malignant transformation to choriocarcinoma. Since most monoclonal antibodies developed so far are murine, administration creates human anti-mouse antibodies, resulting in clinical failure. More recent mouse/human chimeric antibodies or humanized antibodies still possess substantial immunogenicity that makes repeated administration difficult. In the present study, KM mice that can produce completely human monoclonal antibodies were used to prepare hCG-specific human monoclonal antibody. This yielded 8-1A, a human monoclonal antibody capable 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.
Suzuki
N
N
Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Aoki
D
D
Orikawa
K
K
Suzuki
A
A
Susumu
N
N
Tamada
Y
Y
Sakayori
M
M
Tsukazaki
K
K
Mukai
M
M
Kikuchi
H
H
Ishida
I
I
Nozawa
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D015153:Blotting, Western; D006063:Chorionic Gonadotropin / Q000276:immunology*; D006801:Humans; D007120:Immunochemistry; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic
C508886:8-1A monoclonal antibody, human; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006063:Chorionic Gonadotropin