E-Book Overview
Hands-on experts from laboratories around the world describe in step-by-step detail their cutting-edge methods for developing and applying these powerful proteins. The conjugates created by these researchers contain entire monoclonal antibodies, single chain antibody fragments, and cytokines as their carrier ligands. Their toxic portion can include such conventional chemotherapeutics as doxirubicin, such ribosome-inactivating proteins the ricin A chain or saporin, or such bacterial toxins as diphtheria toxin. Also described are a variety of applications that demonstrate the versatility of these agents, including the treatment of primary malignant brain tumors, the generation of selective brain lesions to localize critical functions, and the targeting of the AIDS virus. Authoritative and highly practical, Immunotoxin Methods and Protocols provides today's cancer researchers, neuroscientists, and oncologists with state-of-the-art tools for exploring these powerful biological agents and their rapidly increasing applications.
E-Book Content
BR96 Immunoconjugate
3
1 Development and Activities of the BR96-Doxorubicin Immunoconjugate Ingegerd Hellström, Karl Erik Hellström, and Peter D. Senter 1. Introduction
1.1. Immunoconjugates for Tumor Targeting 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