Antitumor activity of L/1C2-4-desacetylvinblastine-3-carboxhydrazide immunoconjugate in xenografts.
The murine IgG3 monoclonal antibody L/1C2 is reactive with a high percentage of human carcinomas and has preferentially strong reactivity with tumors of squamous differentiation. This antibody was tested for antitumor activity in vitro and in xenograft models as a carbohydrate-linked immunoconjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxhydrazide (DAVLBHYD). The conjugate retained good immunoreactivity and was highly active in a cytotoxicity assay. In human tumor nude mouse xenograft studies, L/1C2-DAVLBHYD antitumor activity was superior to that seen with free drug, free antibody, mixtures of free drug and free antibody, or control DAVLBHYD conjugates prepared with non-tumor-binding IgGs. With well-established tumors, potent antitumor activity was observed, including the ability to specifically regress greater than 400-mg tumors to 0 mg. In some cases, apparent long-term cures were effected. In studies using six different human tumor xenografts, the level of potency of L/1C2-DAVLBHYD was related to L/1C2 antigen expression, although the growth rate probably also contributes to the conjugate sensitivity of the tumors.
Johnson
D A
DA
Connective Tissue and Monoclonal Antibody Research MC620, Eli Lilly and Company, Indianapolis, Indiana 46285.
Baker
A L
AL
Laguzza
B C
BC
Fix
D V
DV
Gutowski
M C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000138:chemical synthesis / Q000627:therapeutic use*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000138:chemical synthesis / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use
C052672:4-desacetylvinblastine 3-carboxyhydrazide monoclonal antibody conjugates; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D014747:Vinblastine