Enhancing the T cell stimulatory capacity of immature DCs

Dendritic cell (DC)-based vaccines form a promising strategy as additional therapy for the treatment of cancer. To this end, we aim to give the patient's immune system a specific signal to recognize and kill the tumor cells while safeguarding healthy tissue.
Although DC-based clinical studies have given promising results, and spectacular tumor regressions have been observed in a minority of patients, overall immunological and clinical responses remain poor. A possible reason for this, is the fact that the matured DCs used for vaccination have an inferior CD4+ and CD8+ T cell stimulatory capacity to induce a good cellular immune respons to break established tolerance. With this project we will investigate novel methods to generate mature, stimulatory DCs with an enhanced T cell stimulatory capacity. This will be performed by electroporating DCs with mRNA encoding stimulatory molecules and by maturing them with TLR ligands.