Antitumor activity of the monoclonal antibody-Vinca alkaloid immunoconjugate LY203725 (KS1/4-4-desacetylvinblastine-3-carboxhydrazide) in a nude mouse model of human ovarian cancer.

The activity of the conjugate of monoclonal antibody KS1/4 with 4-desacetylvinblastine-3-carboxhydrazide (KS1/4-DAVLB-HY) was explored in the OVCAR-3 human ovarian xenograft tumor model. Multiple schedules of KS1/4-DAVLB-HY administration were employed, including a comparison of i.p. and i.v. routes of treatment. When inoculates of 6 x 10(7) OVCAR-3 cells were injected i.p. into female athymic nude mice, untreated control animals had a mean survival of 18-34 days, with the development of massive ascites and large intraabdominal tumors. Significant increases in survival were observed in KS1/4-DAVLB-HY conjugate-treated animals with all schedules utilized. Parallel therapy with equivalent doses of free DAVLB-HY or a non-antigen-binding immunoconjugate did not significantly increase the survival of the animals. These data demonstrate that the immunoconjugate KS1/4-DAVLB-HY significantly increases the survival of OVCAR-3 tumor-bearing mice and indicates that this immunoconjugate may be useful in the treatment of human ovarian cancer.