Efficacy and specificity of vindesine monoclonal anti-carcinoembryonic antigen conjugate with nine human cancer cell lines.
To establish a model for evaluation of the efficacy and specificity of monoclonal anti-CEA-vindesine (VDS) conjugates, we have characterized 10 human tumor cell lines (7 colorectal cancer and 3 lung cancer) with 3 monoclonal antibodies that recognize different epitopes of the CEA molecule. Immunocytochemistry indicated high, medium, low, or no capacity of the cell lines to bind antibody and express CEA. We used 125I-labeled antibodies to quantitate the number of antibody molecules binding per cell. The most thoroughly evaluated monoclonal antibody, 11-285-14, which is nonreactive with nonspecific cross-reacting antigen and is known to localize in xenografts and in cancer patients, was selected for assessment of VDS-conjugate efficacy. This was evaluated by 24- and 72-hour exposure in tritiated uridine microcytostasis assays with nine of the cell lines. Conjugates were shown to retain anti-CEA activity after conjugation, and the efficacy of VDS-11-285-14 in vitro was found to be correlated with target antigen expression, except with two lines that were resistant to free drug. Absorption of VDS-11-285-14 with purified CEA resulted in loss of efficacy in positive cell lines, thereby giving a further indication of the selectivity of conjugate efficacy.
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D000918:Antibody Specificity; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D012004:Rectal Neoplasms / Q000188:drug therapy; D014529:Uridine / Q000378:metabolism; D014751:Vindesine / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D014751:Vindesine; D014529:Uridine