From molecular optimization to therapy combination : novel strategies to improve cancer DNA vaccines

Until now, DNA vaccination against cancer failed to demonstrate a relevant activity in clinic or in a therapeutic setting in preclinical models. This thesis shows two strategies to improve DNA vaccine activity. The first is the optimization of the plasmid itself, by codon optimization and a rational antigen choice. The second is the combination of the vaccines with other complementary therapies: 1) Immune checkpoint blockade in P815 mastocytoma. 2) Oncolytic virus in B16F1 melanoma. 3) Tumor resection in orthotopic GL261 glioblastoma. The common outcome was the dramatic increase in survival in the combination group, explained by the presence of active and antigen-specific T cells in the tumor. Hence, vaccine optimization and rational combined therapies overcome the current limitations of DNA vaccines. This work opens the way to new therapies for the treatment of cancer patients.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201