RNA transfer and its use in dendritic cell-based immunotherapy.
RNA is a key macromolecule for the mobilisation and interpretation of genetic information. Research has sought to exploit the inherent properties of RNA, such as the direct production of proteins in the cytoplasm without the need for nuclear translocation. This property makes the delivery of genes into postmitotic cells especially attractive. Recently, RNA transfer into postmitotic dendritic cells (DCs) has emerged as a potential new therapeutic agent in the area of immunotherapy. DCs are the most important regulators of the immune system. Thus, transfecting DCs with RNA allows the specific manipulation of immune responses and, thereby, the treatment of a variety of diseases, such as cancer. Preclinical studies have demonstrated that RNA-transduced DCs efficiently stimulate antigen-specific T cell responses in vitro and in animal tumour models. In addition, the clinical data from Phase I and II trials of tumour patients indicate that RNA-transduced DCs represent a promising approach for the development of future vaccination strategies. The use of RNA molecules as therapeutic agents is a relatively new approach in the treatment of diseases, such as cancer, but has received increasing attention during the past decade. Especially in the field of immunotherapy, the inherent properties of RNA molecules in combination with immunostimulating dendritic cells (DCs) are being investigated at present for their beneficial therapeutic effect. Immunotherapy is based on the stimulation of the patient's immune system to recognise and eliminate infected cells or tumour cells in an antigen-specific manner. Current approaches focus on the stimulation of CD8(+) cytotoxic T lymphocyte responses, as well as on the induction of CD4(+) T helper cell responses, in order to obtain optimal and sustained immune responses capable of eliminating altered cells. This review mainly focuses on the potential use of RNA-transduced DCs as a therapeutic strategy in the treatment of cancer, as current studies on the treatment of infectious diseases are just beginning.
Gust
Tatjana C
TC
Charité, Laboratory of Inflammation and Gene Therapy, Department of Trauma and Reconstructive Surgery, Krahmerstrasse 6-10, 12207 Berlin, Germany.
Zenke
Martin
M
D000818:Animals; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003713:Dendritic Cells / Q000276:immunology*; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology; D012343:RNA, Transfer / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
D012343:RNA, Transfer