ARCOBALENO cell therapy to treat pediatric cancer patients

Abstract

Immunotherapy has been considered a breakthrough in cancer treatment in the past decade. Immune checkpoint inhibitors and Chimeric Antigen Receptor T cells (CAR-T cells) have entered clinical practice and achieved promising success rates in some tumor type, such as melanoma and acute lymphoblastic leukemia, and are under clinical tests in many other cancer types CAR-T cells, or similar type of treatments, account for ex-vivo modification of patients-derived immune cells to induce specificity towards tumor cells. As this strategy is characterized by the use of living cells, many limiting factors, not only related to the method of action but also to the production of the therapy, are holding back the application of this approach. First of all, a fully personalized production is required for every patient, stretching the time from availability for treatment to the possibility to receive it. Moreover, the number and fitness of cancer patient-derived immune cells, does not always meet the quality control requirements essentials to produce cell therapy products. Those production hurdles cause delay and decrease the chances for a successful administration of a potentially curable treatment. The aim of this thesis is to shed a light on the use of an alternative allogeneic source of immune cells for the generation of cell therapy product, and overcome some of the problems that have obscured the potential of cell therapy. More in detail, the use of umbilical cord blood (CB) derived immune cells, and the possibility to modify them with novel gene augmentation and gene-editing techniques, is the core of this dissertation.