Polymer-Based DNA Delivery Systems for Cancer Immunotherapy

David, Ayelet; Golani-Armon, Adi

The use of gene delivery systems for the expression of antigenic proteins is an established means for activating a patient’s own immune system against the cancer they carry. Since tumor cells are poor antigen-presenting cells, cross-presentation of tumor antigens by dendritic cells (DCs) is essential for the generation of tumor-specific cytotoxic T-lymphocyte responses. A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter summarizes the physicochemical properties and biological information on polymer-based non-viral vectors used for targeting DCs, and discusses the main challenges for successful in vivo gene transfer into DCs.