Antibody Therapy

 

 

• Antibodies and Therapy - In 1895 Hericourt and Richet described the first trials in which cancer cells were injected into animals to raise an antiserum for treating the patient. Their results seemed very promising and several patients with different types of advanced cancer were treated, each receiving an individual, tailor-made antiserum. None of them was cured, but they showed significant improvements in their symptoms. During the early 1900's many workers repeated these trials, but found inconsistent and contradictory results, leading to the conclusion in 1929 that "nothing may be hoped for at present in respect to a successful therapy from this direction".

• Historical Perspective to Humanized Antibodies - A century ago, Paul Ehrlich proposed that antibodies could be used as "magic bullets" to target and destroy human diseases. This vision is still being pursued today since antibodies combine specificity (the ability to exquisitely discriminate diverse harmful molecules) and affinity (the ability to tightly lock onto those targets) with the ability to recruit effector functions of the immune system such as antibody- and complement-mediated cytolysis and antibody-dependent cell-mediated cytotoxicity (ADCC). Alternatively, a "toxic payload" (such as a radioactive element or a plant toxin) attached to the antibody can be accurately delivered to the target. This makes them suitable for homing in on and killing cancer cells, infectious diseases (bacteria, viruses and their toxins) as well as modulating the immune system by binding and inhibiting or enhancing its regulatory molecules and thus curing autoimmune and inflammatory diseases.

• Reshaping Antibodies for Therapy By Edward G. Routledge, Scott D. Gorman & Mike Clark - Since the early description of monoclonal antibodies by Kohler and Milstein in 1975 there has been considerable interest in their adoption for human serotherapy. A number of issues have been raised, and principle amongst them is the selection of antibodies with appropriate specificities for therapy, and the next major issue is whether such antibodies are then functional in vivo, but both of these issues are outside the scope of the discussion in this chapter. Rather, this chapter deals with an important secondary issue which is the problem of the antiglobulin response, encountered when rodent antibodies are used for prolonged human therapy. This problem derives from the fact that although antibodies show some conservation there are many sequence differences between rodent immunoglobulins and human immunoglobulins. The injection of rodent monoclonal antibodies into a human recipient usually results in an antiglobulin response which is detectable at about 8-12 days and reaches a peak at about 20-30 days. The presence of the antiglobulin response usually precludes treatment beyond 10 days and the rapid onset of a secondary response prevents retreatment at a latter date.

• Monoclonal Antibody Therapy - Monoclonal antibody therapy is a form of passive immunotherapy because the antibodies are made in large quantities outside the body (in the lab) rather than by a person’s immune system. These treatments do not require the person’s immune system to take an "active" role in fighting the cancer.

• Neutralizing Antibodies - Over the past decade, there has been debate among MS specialist physicians about the role of neutralizing antibodies (NAbs) in treatment decisions and treatment outcomes. This document summarizes the basic issues in the scientific literature.