Cancer immunotherapy

Abstract

Both of this year’s Nobel Prize Winners: James P. Allison and Tasaku Honjo made a disruptive discovery concerning the mechanisms of repressing the immunological response. They identified and characterised two different proteins: CTLA-4 and PD-1. They can be found on the surface of T lymphocytes and they are immunological checkpoints. James P. Allison stated that for the complete immunological activation, apart from the recognition of antigen by T-cell receptor, the interaction with proteins B7-1 (CD80) and B7-2 (CD86) acting as an accelerator/costimulator is also crucial. The protein CTLA-4 controls this process competitively repressing the joining of these proteins to T-cell receptor CD28, which blocks their full activation. Another activation mechanism was discovered by T. Honjo, who identified immunoreceptor PD-1, appearing on T-cells, and its ligands PD-L1 and PD-L2. Their expressed occurs on the surface of various cells, and what seems to be the most important, also on cancer cells. The interaction of PD-1 receptor with its ligands leads to the inhibition of the immunological reaction. The merit of this year’s Nobel Prize Winners is also presenting that blocking of CTLA-4 and PD-1 checkpoints by specific antibodies allows to gain the desirable T lymphocytes activity, which results in cancer destruction. James P. Allison`s and Tasaku Honjo`s research created the structure of new drugs – immunological inhibitors of control points: CTLA-4 and PD-1 checkpoints immunological and PD-L1/L2 ligands inhibitors. These drugs (monoclonal antibodies) in many cases resulted in a spectacular regression of cancer disease (major tumor regression). The results so far have been so impressive that FDA approved their application in therapy of various advanced cancers, such as: metastatic stage, lung cancer, kidney cancer, bladder cancer, head and neck cancer and other cancers.