Electroporation as a method of choice to generate genetically modified dendritic cell cancer vaccines.

Abstract

In the last few decades, immunotherapy has emerged as an alternative therapeutic approach to treat cancer. Immunotherapy offers a plethora of different treatment possibilities. Among these, dendritic cell (DC)-based cancer vaccines constitute one of the most promising and valuable therapeutic options. DC-vaccines have been introduced into the clinics more than 15 years ago, and preclinical studies showed their general safety and low toxic effects on patients. However, their treatment efficacy is still rather limited, demanding for novel avenues to improve vaccine efficacy. One way to potentially achieve this is to focus on improving the DC-T cell interaction to further increase T cell priming and downstream activity. A successful DC-T cell interaction requires three different signals (Figure 1): (1) Major Histocompatibility Complex (MHC) and antigen complex interaction with T cell receptor (TCR) (2) interaction between co-stimulatory molecules and their cognate ligands at the cell surface and (3) secretion of cytokines to polarize the immune response toward a Type 1 helper (Th1) phenotype. In recent years, many studies attempted to improve the DC-T cell interaction and overall cancer vaccine therapeutic outcomes by increasing the expression of mediators of signal 1, 2 and/or 3, through genetic modifications of DCs. Transfection of genes of interest can be achieved through many different methods such as passive pulsing, lipofection, viral transfection, or electroporation (EP). However, EP is currently emerging as the method of choice thanks to its safety, versatility, and relatively easy clinical translation. In this review we will highlight the potential benefits of EP over other transfection methods as well as giving an overview of the available studies employing EP to gene-modify DCs in cancer vaccines. Crucial aspects such as safety, feasibility, and gene(s) of choice will be also discussed, together with future perspectives and opportunities for DC genetic engineering.