RNA-based immunotherapy of cancer: role and therapeutic implications of dendritic cells

Abstract

Cancer immunotherapy aims at eliciting an immune response directed against tumor antigens to help fight off residual tumor cells and, thereby, improve the survival and quality of life of cancer patients. Different immunotherapeutic approaches share the use of dendritic cells (DCs) to present tumor-associated antigens to T lymphocytes. DCs are specialized for antigen presentation, and their immunogenicity leads to the induction of antigen-specific immune responses. Ex vivo-generated DCs can be loaded with antigens and re-infused to the patients or they can be used for the ex vivo expansion of anti-tumor lymphocytes. Alternatively, methods exist to target antigens in vivo without the need for ex vivo cell manipulations. DCs loaded ex vivo with RNA can be administered safely and might prove to be an asset for producing antigen-specific immune responses. Furthermore, these observations have led to clinical trials designed to investigate the immunological and clinical effects of RNA-pulsed DCs administered as a therapeutic vaccine in cancer patients. However, selection of the antigen, methods for introducing tumor-associated antigens into MHC class I and II processing pathways, methods for isolation and activation of DCs and route of administration are the parameters to be considered for designing and conducting clinical trials with phenotypically altered DCs. The enhanced RNA transfection efficiency and DC maturation would further improve antigen processing and presentation and T-cell costimulation, resulting in the induction of heightened anti-tumor immune responses. Therefore, DCs pulsed with RNA continues to hold promise for cellular immunotherapy.