Cancer and autoimmune diseases affect more than 5 million people in France and represent major causes of mortality and morbidity. The recent advent of immunotherapy has given new hope for the treatment of these complex pathologies. These biological treatments act in a targeted way on the patient's immune system to help him fight his disease. Despite some notable successes (e.g. PDL1-PD1), the diversity of targets of these drugs remains limited and many patients do not respond to treatments. It is therefore crucial to develop new immunotherapies to better treat and cure these diseases. Thanks to our nearly 30-year research experience on a major biological pathway for activating the immune response, the MICA/B-NKG2D pathway, we have recently been able to develop several new antibodies and small molecules targeting this pathway. The latter can be activated in the case of cancer, or inhibited in the case of autoimmune diseases. The effectiveness of our reagents has been validated by different cellular, biochemical and biophysical methods. We now propose to transfer these new tools to a therapeutic application in humans, going through all the steps necessary for pre-clinical validation and the start of clinical trials in humans.