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.