IV.

Problems with Monoclonal Antibodies

When MAbs were first developed, they were hailed as “magic bullets,” a therapy that would target and attack only disease-causing cells or substances in a patient while causing no side effects. Effective uses for MAbs remain limited, however, for several reasons. MAbs are usually created using mouse B cells. When used in humans, these MAbs are often recognized by the immune system as foreign proteins. As a result, the body produces antibodies that attack the MAbs and eventually neutralize them. The first dose of a MAb is often the most effective since it takes up to two weeks for the immune system to create an antibody to fight off a new foreign substance. During this period, the MAb is able to perform the job for which it was created. Once antibodies against the MAb have been produced, however, the effect of the MAb diminishes entirely. A major issue with many MAbs is that they can precisely identify and locate their intended antigen targets, but when they reach the targets they are unable to neutralize or destroy the antigens.

Other problems are specific to immunoconjugates. For example, if the payload a MAb carries is delivered to the wrong part of the body, side effects can occur. In other cases, the payload may fall off the MAb and travel freely throughout the body randomly harming cells. Therapies that use immunoconjugates to treat solid tumors face a different obstacle due to the physical makeup of these tumors. Unlike other types of cell growth, the blood vessels that feed solid tumors curve sharply, sometimes looping, through the tissue mass. This kind of structure makes it difficult for antibodies to enter the tumor. Those MAbs that do penetrate the tumor must then cross blood vessel walls to reach the tumor cells and destroy them. The unusually high blood pressure maintained in solid tumors, however, often prevents MAbs from reaching their destination.