Immunotherapy and antibody-drug conjugates

Activating the immune system

Immunotherapies combat cancer using the body's own immune system. Researchers are developing antibodies that are geared to the characteristics of the cancer cell. They specifically 'lure' the body's own killer cells to the tumor and activate them, so that the cancer cell is recognized by the body's own immune system as hostile and then destroyed.

Antibodies as drug transporters

The fact that antibodies can selectively recognize very specific structures in the body, with which they interact and bond, makes them attractive for use in transporting active substances straight to the precise focus of a disease. Oncology researchers at Bayer use this mechanism in the development of what are known as antibody-drug conjugates (ADCs). An antibody is used to transport a cytotoxic (= cell-killing) substance direct to cancer cells and release it inside the cells. In this way the healthy cells are largely spared the toxic side-effects that occur with traditional chemotherapy

ADCs consist of three different components: the antibody, a cytotoxic active ingredient (the toxophore), and a so-called 'linker' which connects the antibody and the toxophore. The researchers choose an antibody that recognizes and binds to certain protein molecules ('tumor markers') on the surface of tumor cells. This binding process triggers a mechanism which transports the ADC inside the cell, where the cytotoxic 'payload' (toxophore) is unloaded and can unleash its destructive effect: important cell functions are blocked, and this leads to programmed cell death (apoptosis). However, it is essential for the success of a therapy with ADCs that the conjugate does not lose its toxic payload as its passes through the body, and does not release it until it is inside the cancer cell. The 'linker' is therefore designed in such a way that it can only be split inside cancer cells.