A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R
tumor cells treated with
cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd
membrane glycoprotein (HG-90) which is expressed on in vitro cultured
hepatoma cell lines AH66 and AH66R. A
monoclonal antibody was prepared to the
anthracycline drug daunomycin, and it also reacted with
adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized
daunomycin/
adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the
therapeutic effect of the A8C bispecific antibody with
adriamycin treatment and compared it to the effect of the bispecific antibody to which
adriamycin had been conjugated via an
albumin (Alb) bridge. The
therapy model used was the
tumor AH66R in Donryu rats.
Tumor bearing rats had their subcutaneous
tumors resected on day 10, a time when distant
metastases were present. After the surgical resection of the
tumor the rats were injected intravenously for two cycles with the
bispecific antibodies, followed by the administration of
adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight
therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "
tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and
drug treatment. This suggests that the bispecific antibody/
drug treatment is potentially more beneficial in the suppression of distant
metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local
drug concentration of unmodified
adriamycin.