Development and Activities of the BR96-Doxorubicin Immunoconjugate

The use of antibodies to selectively destroy tumors has attracted attention since Paul Ehrlich's dream about "magic bullets," and it gained support from the demonstration by Pressman in the 1950s that antibodies can be employed to deliver radioisotopes to tumors in rodents. The promise of this approach received a strong boost when Köhler and Milstein introduced monoclonal antibody (MAb) technology in the 1970s (1). However, the clinical success of unmodified MAbs or MAbs conjugated to drugs, radioisotopes, or toxins in the treatment of tumors has been modest so far. The primary exceptions are the use of MAbs targeting the HER2 growth factor receptor in breast carcinomas (2) and MAbs to treat B-cell lymphomas (3, 4). Encouraging results have also been obtained when a MAb reacting with a differentiation antigen expressed on colorectal carcinomas was given to patients who were at high risk of tumor recurrence following primary surgery (5).