In the context of cancer therapy, antibodies produced outside the patient are used which are directed against secreted factors, membrane receptors or surface antigens of tumor cells. In order to avoid an immune reaction against the foreign protein in the patient, the domains outside the antigen binding region are replaced by the domains of human antibodies. One speaks of a humanization of the antibodies.
The video shows the following therapy principles:
- Antibodies that are directed against extracellular receptor ligands can block their binding to receptors of the tumor cell and thus inhibit their effect. An example is the antibody Bevacizumab (Avastin), which is directed against the vascular endothelial growth factor (VEGF). By blocking receptor binding, Avastin inhibits angiogenesis in tumor tissue.
- By binding to extracellular domains of receptors, antibodies can inhibit the action of these receptors and block signaling pathways that activate cell division. An example is Trastuzumab (Herceptin), an antibody that is directed against the EGF receptor homolog HER2/Neu on cells of breast cancer. ERBB2 is the gene that encodes HER2/Neu. Patients in whose tumors the ERBB2 gene is amplified are treated with Herceptin.
- Via their constant domains, antibodies bound to tumor cells can activate the complement system and can bind to Fc receptors on cells of the non-clonal immune system (NK cells, macrophages). The monoclonal antibody Rituximab (Rituxan) reduces the number of B cells after binding to CD20 by activating the complement system (CDC) and cells of the non-clonal immune system (antibody-dependent cell-mediated cytotoxicity, ADCC; antibody-dependent cellular phagocytosis, ADCP). Rituxan is used in the treatment of non-Hodgkin lymphoma.
- Antibodies directed against cell surface antigens of tumor cells can be coupled to cell poisons or radioactive substances that attack the tumor cell. In this case the antibodies serve as specific means of transport for the coupled active substance. In order to ensure the uptake of a toxin into the cell, the antibody must be directed against receptors that are ingested by endocytosed. One example is the anti-CD33 antibody Gemtuzumab (Mylotarg) coupled with the fungal poison calicheamicin, which is used in the treatment of acute myeloid leukemia (AML). Ipritumomab (Zevalin) is currently the only antibody linked to a radioactive isotope in clinical use. The isotope 90Y of the transition metal yttrium is a strong beta emitter with a half-life of 64 hours. After binding to the B-cell-specific antigen CD20, 90Y causes massive DNA damage that leads to apoptosis. Zevalin may be used in the treatment of non-Hodgkin lymphoma.
