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Immuno-Conjugates: New Prospects on Old Principles, pp. 189-197 $100.00
Authors:  M.F. Barginear, D.R. Budman, The Tisch Cancer Insitute, The Mount Sinai School of Medicine, New York, NY, and others
Paul Ehrlich received the 1908 Nobel Prize in Medicine for his work in
Immunology [1]. 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 [2]. 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 [3]. 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 [4]. 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 [9]. Besides efficacy, the
off target effects of these agents are limited which adds to their attractiveness. 

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Immuno-Conjugates: New Prospects on Old Principles, pp. 189-197