Immuno-Conjugates: New Prospects on Old Principles, pp. 189-197
Authors: M.F. Barginear, D.R. Budman, The Tisch Cancer Insitute, The Mount Sinai School of Medicine, New York, NY, and others
Abstract: Paul Ehrlich received the 1908 Nobel Prize in Medicine for his work in Immunology . He stated “The immune substances … in the manner of magic bullets, seek out the enemy.” As such, he predicted the emergence of targeted agents which have lessened effects on host tissue. However, serotherapy was limited by the lack of appropriate targets, the inability to make discrete antibodies with high specificity in large quantities, and the reproducibility of the characteristics of the poly-antisera. In the late 1970’s, George Köhler and César Milstein fundamentally changed Immunology by developing the technology of hybridomas, the production of a desired specific antibody in large amounts . These investigators showed that antibody-producing cells, of any specificity, could be fused with a myeloma cell line and create an unlimited amount of monoclonal antibodies (mAb) carrying that specificity . This has led researchers, clinicians, and especially biotechnology companies to focus on new diagnostic and therapeutic agents. Oncology has been a major area of focus for mAb-based diagnostic and therapeutic agents, primarily because of the overexpression of numerous antigens on cancer cells compared with normal, non-cancerous cells and tissues. As a single agent, trastuzumab (Herceptin®, Genentech) has remarkable activity in Her2/neu over expressing breast cancers both in the adjuvant and in the metastatic settings . However, the majority of patients with metastatic HER2 overexpressing breast cancer who initially respond to trastuzumab develop resistance within one year of initiation of treatment, and in the adjuvant setting, patients may still progress despite trastuzumab-based therapy [5-8]. In analogous manner, Rituximab (Rituxan®, Genentech) has been a major clinical advance in B-cell lymphomas . Besides efficacy, the off target effects of these agents are limited which adds to their attractiveness.