Enhancement of Gene Gun-Induced Vaccine-Specific Cytotoxic T-Cell Response by Administration of Chemotherapeutic Drugs

Abstract

Because they specifically kill dividing cells, untargeted chemotherapeutic drugs such as platin derivatives, antimetabolites or topoisomerase inhibitors for example impact the immune system resulting in more or less profound transient lympho- and/or myelo-ablations in treated patients. Although this side effect of chemotherapeutic regimens could be assumed as immunosuppressive, it surprisingly appeared to eventually potentiate vaccination. By demonstrating that regulatory T-cells that mediate inhibition of immune responses proliferate more than other CD4-positive T-cells, we identified a possible mechanism underlying the vaccine-enhancing feature of certain chemotherapeutic anticancer regimen. The combination of cytostatic drugs and Gene Gun vaccination is of great interest in particular for the enhancement of antitumor, including “anti-self,” vaccination strategies to treat cancer. Here we describe the effect of Gemcitabine, a standard chemotherapeutic drug, on human and mouse regulatory T-cells in vivo and present the methods allowing to trigger and detect an enhanced cytotoxic T-cell immune response using Gene Gun vaccination after Gemcitabine administration.