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.
Apelgren
L D
LD
Department of Connective Tissue and Monoclonal Antibody Research, B.J, Lilly Research Laboratories, Indianapolis, Indiana 46285.
Zimmerman
D L
DL
Briggs
S L
SL
Bumol
T F
TF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
C055183:4-desacetylvinblastine hydrazide-monoclonal antibody KS1-4 conjugate; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; C055170:4-desacetylvinblastine hydrazide; D014747:Vinblastine