Coupling a preactivated daunorubicin derivative to antibody. A new approach

Many procedures have been reported for coupling anthracycline drugs to antibody for drug targeting. But they either yield conjugates with lower pharmacological activity or antibodies which have lost much of their immunological specificity. The use of glutaraldehyde for coupling saves both pharmacological and immunological activities but it causes a considerable polymerization of the antibody which is undesirable for in vivo use. We report a new coupling procedure which uses an activated daunorubicin derivative which is later added to the antibody. Using this procedure for daunorubicin coupling to monoclonal anti-CEA we found no significant polymerization of the conjugate and a full recovery of the pharmacological activity as tested in vitro on CEA producing human colon adenocarcinoma cells. The activated drug was found stable for one week at 25 degrees C and the whole coupling procedure is highly reproducible.