Monoclonal antibodies against immune checkpoints in immunotherapy of cancer patients

Abstract

Since 1975, when Koehler and Milstein had established the technology for the production of monoclonal antibodies, they were applied in numerous scientific experiments as well as for diagnostic and therapeutic purposes. In the late 90s of the last century, monoclonal antibodies which act by blocking surface receptors on abnormal cells, have proven to be very effective in the treatment of diseases such as breast cancer (trastuzumab) and colorectal cancer (cetuximab, panitumumab). After decade we observe a dynamic development of cancer immunotherapy involving monoclonal antibodies targeting immune checkpoints of immune response. The use of anti-CTLA-4 (ipilimumab), anti-PD-1 (niwolumab, pembrolizumab) or anti-PD-L1 (MPDL-3280, MEDI-4736) is intended to remove an anergy effector T cells induced by tumour cells or by antigen presenting cells. This type of therapy often results in long-term disease control and in development of a specific immune response in such malignancies as melanoma, non-small cell lung cancer, kidney and pancreatic cancer. They are generally less toxic than chemotherapy, but the treatment is associated with quite frequent autoimmune phenomena.