New directions in immunopharmacotherapy.

Abstract

The application of antibodies for immunotherapy was documented as early as 1890 (von Behring and Kitasato 1890). In the past, polyclonal antibodies found in antiserum against specific antigens were used in passive immunization strategies to combat infectious diseases such as hepatitis B and HIV (Sawyer et al. 1998; Jacobson 1998). While this approach has merit, it is hampered by several unwanted side effects, including the risk of viral contamination, serum sickness, anaphylaxis (nonhuman serum) and, importantly, the difficulty of making standardized batches of antibody to insure reproducibility and proper dosing. A milestone was reached when the production of homogeneous monoclonal antibodies (mAbs) with defined specificity and high affinity became a reality through hybridoma technology, developed by Kohler and Milstein in 1975. As a result, thousands of mAbs against different antigens have been generated and used in a wide variety of biological studies. Additionally, hybridoma technology ushered in the concept of replacing polyclonal antibodies with mAbs as therapeutic drugs (Coons 1995; Scott and Welt 1997; Vaswani and Hamilton 1998). Indeed, with well-defined specificity and better reproducibility, mAbs have been touted as “magic bullets” in the fight against disease. Our research efforts have been aimed at utilizing antibodies, both in passive administration and as generated in vivo by an immune response, for cancer treatment and in the treatment of cocaine abuse. We describe the details and directions of our immunopharmacological studies in these areas.