One antibody, two points of attack - this slogan can be used to describe the concept behind a class of active ingredients that, due to their enormous medical potential, has triggered a veritable gold rush mood in the executive floors of the pharmaceutical industry: bispecific antibodies. Antibodies are part of the immune system and use the two arms of their Y-shaped structure to bind to a target molecule, the so-called antigen. Unlike the natural antibodies, which only ever recognize a single antigen and are therefore monospecific, the bispecific antibodies produced in the laboratory recognize two antigens and can therefore also perform two tasks. The wise choice of these antigens - and that is the reason for the new euphoria - opens up therapeutic possibilities that go far beyondwhat can be expected from the pure combination of two antigen binding sites in a single molecule. The spectrum ranges from the mobilization of the immune system to the double blockade of metabolic pathways to the networking of receptors or other biomolecules. In the fight against coronaviruses, but especially in cancer medicine, expectations are high.
The current prime role of bispecific antibodies there is to create immune cells with a killer function - so-called cytotoxic T cells - in the immediate vicinity of the tumor cells. To do this, the bispecific antibodies make contact with the killer cells via one antigen binding site and with the tumor cells via the other binding site. Taken side by side in tow, the two cells come so close that the killer cells are activated and can give the tumor cells a fatal blow. This means that these bispecific antibodies work in a similar way to the so-called CAR-T-cell therapy, which has also attracted attention in cancer medicine for years - although the bispecific antibodies can score some pluses for themselves.
In CAR therapy, the killer T cells search for the tumor cells with an antibody-like protein, which, however, first has to be installed on their surface. This happens in the laboratory and takes time. The CAR therapy must also be tailor-made for each patient and is strictly regulated. A bispecific antibody can in principle be used for every patient who carries the corresponding antigen on his tumor cells and, if necessary, could be used immediately. CAR cells are also more difficult to control because they are a "living drug" and multiply in the patient's body. In the event of problems, they cannot simply be put back on the leash. A bispecific antibody, on the other hand, disappears from the blood after hours or days. Nevertheless, bispecific antibodies must also know how to behave.They are not natural molecules, but designer molecules from the laboratory. Many candidates fail because of the side effects.
The first bispecific antibody that follows the principle outlined was approved in 2009 and withdrawn from the market in 2017. In 2014, blinatumomab, a second antibody based on this therapeutic principle, was approved. It is used for forms of blood cancer. There are currently more than a hundred different bispecific antibodies in clinical development. There are also efforts to recruit not only cytotoxic T cells for an attack on the immune system, but also so-called NK cells or natural killer cells. They would activate another level of immune defense.