On the road to personalized immunotherapy: an unexpected journey

Abstract

Cancer immunotherapy has transformed the treatment for advanced cancers. However, durable responses to the treatments are rare events. To further improve the efficacy of current cancer immunotherapies, it is necessary to find ways to predict which patient is most likely to respond or not to the treatment, who is likely to eventually relapse, which resistance mechanisms will arise and how to overcome these mechanisms. To achieve those goals we generate two new model systems to study the interaction between tumor cells and immune cells, for the individual patient: the coculture and the HANSolo platforms. The coculture is a platform to train the immune cells of the patient to recognize and kill the tumor cells. First, starting from a biopsy, we generate tumor organoids, a three-dimensional model of the patient tumor that can be cultured in the laboratory. Next, the patient immune cells, isolated from a vial of blood, are trained (in coculture) with the tumor organoids, to become reactive against the patient tumor cells. We demonstrated the feasibility and physiological value of this approach. Furthermore, we explore possible applications of this model system in the development of new drugs. A reactive immune population is powerful, but also dangerous; it is important to know the target of that reactivity, to avoid any side effects. HANSolo is a platform that combines the use of patient derived material and new sequencing technology to discover what are the molecules recognized on the surface of a tumor cells by the immune system.