Combined Cancer Immunotherapy Based on Immunostimulant Monoclonal Antibodies
Clínica Universidad de Navarra is playing key role in the development of clinical trials of different immunomodulatory agents based on monoclonal antibodies (immunostimulant monoclonal antibodies). These agents act by depressing inhibitory mechanisms of the immune system (e.g., anti-PD-1 and anti-CTLA-4) or by acting as agonists on receptors that activate the immune system (CD137, OX40, LAG-3). In order to optimize their antitumor effects, we are testing combinations in treatment strategies that look for therapeutic effects of greater synergy by combining the following: (i) several agents of this type, (ii) intra-tumor injection of pro-immunogenic substances or viral vectors, (iii) transitory adoptive-cell therapy with genetically modified T lymphocytes by means of electroporation of synthetic mRNA and siRNA, and (iv) external radiotherapy and brachytherapy strategies. A large part of our efforts are focused on understanding the molecular and cellular mechanisms involved in the synergetic effects achieved by means of these treatments and in their translation to pioneering clinical trials in patients with advanced cancer. To do this, we have animal models and models of valuable samples from patients treated in clinical trials that are in progress or that have already been completed.