Resumen
In first clinical trials, vaccinations against tumor-associated antigens (TAA), such as Alpha-Fetoprotein (AFP) using antigen presenting cells, such as dendritic cells (DC), failed to achieve effective immune responses towards hepatocellular carcinoma (HCC). CD40Ligand is a potent immune checkpoint, which can increase the antitumoral immune response of DC. In this study, a subcutaneous vaccination with DCs, which were transduced with AFP-coding adenoviruses and an intratumoral treatment with DCs, which were transduced with CD40L-coding adenoviruses, induced an antitumoral immune response and led to complete remissions and long-term survival in 62% of mice with established HCC. Combined strategy causes rapid and profound changes in the tumor environment with enhanced Th1-cytokine expression, strong tumor infiltration of cytotoxic T lymphocytes and DC, and higher tumor apoptosis, leading to effective tumor regression of HCC. Thus, intratumoral CD40L co-stimulation represents a promising tool for improving tumor-antigen DC-based immunotherapy of HCC.