Background. Murine monoclonal antibodies (MoAb) potentially can be use
d in the radioimmunodetection and radioimmunotherapy of cancer. Howeve
r, the administration of these radiopharmaceuticals to humans often le
ads to induction of human anti-murine antibodies (HAMA). HAMA has many
disadvantages, which could decrease efficacy of the murine MoAb. The
purpose of this work was to produce human monoclonal antibody against
a human ovarian cancer cell surface antigen (OCCSA), which was not pre
sent in normal ovarian cells. This 200-kilodalton OCCSA also was used
in the present study for characterizing the human monoclonal antibody.
Methods. Human monoclonal antibodies were produced in vitro by fusion
of mutant myeloma cells, selected from GM1500, with human lymphoid ce
lls immunized in vitro with purified OCCSA. The human monoclonal antib
ody was characterized using the following techniques: sodium dodecyl s
ulfate-polyacrylamide gel electrophoresis (SDS-PAGE), native-PAGE, Wes
tern blotting followed by protein-A gold staining, immunodiffusion ass
ays, and fluorescent antibody assays. Results. Human monoclonal antibo
dy, TC5 (immunoglobulin G1), was produced and purified. It was found t
o be specific for ovarian cancer, while also reacting with an early st
age breast cancer. TC5 did not react with any normal (i.e., nonneoplas
tic) cells of the ovary, uterus, cervix, endocervix, or fallopian tube
, nor did it react with normal lung, heart, pancreas, liver, or breast
tissue.Conclusion. Human-human hybridomas produced human monoclonal a
ntibody against OCCSA. The human monoclonal antibody, TC5, was specifi
c for ovarian and breast cancer. TC5 did not react with any normal tis
sue tested. Future work will focus on the in vivo characterization of
the human monoclonal antibody, after labeling with radionuclides. Canc
er 1994; 73:1098-104.