In order to establish human monoclonal antibodies to any sort of antig
ens efficiently, we have made following two approaches. Our first appr
oach is to improve cell fusion frequency. By improving our previous me
thod for production of human hybridomas, we obtained higher frequency
(1/700 vs. 1/5500) compared with our previous method by adding irradia
ted myeloma cells to culture of fusion cells and modifying the selecti
ve medium. Our second approach is to use a SCID-hu mouse for immunizat
ion. Since the injection of human PBL can result in the stable long-te
rm reconstitution of a human immune system in SCID mouse, we tried to
immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse
, we obtained human IgG antibodies to KLH. Additionally, we succeeded
in establishing human B lymphoblastoid cell lines which produced antib
odies specific to KLH. These methods will open new prospects for the d
etection and therapy of cancer.