Overcome the resistance to immune checkpoint targeted antibodies by enhancing the tumor immunogenicity

Immunotherapies using monoclonal antibodies antagonizing T-cell co-inhibition receptors (“checkpoint blockers”) have been revolutionizing oncology for the past 10 years. They have led to significant gains in overall survival in many cancers and are now considered a cure for some patients with metastatic cancers previously considered incurable. Moreover, they are radically changing our understanding of cancer by demonstrating that it can be considered as a dysimmune disease. However, these first generations of immunotherapies are not effective in all patients. A major challenge is therefore to better understand the mechanism of action of these treatments in humans in order to overcome resistance to their effectiveness. Several therapeutic approaches are underway to try to make these treatments more effective. One of them consists of trying to make tumors more visible to the immune system or “immunogenic”. Intratumoral immunotherapy is one of these emerging strategies that aims to use the tumor as its own vaccine by injecting immunostimulant therapies directly into the tumor. The development of these approaches raises new challenges in clinical research but their pre-clinical rationale raises hopes that they will make more patients respond to immunotherapy.