RNA transfer and its use in dendritic cell-based immunotherapy

被引:7
作者
Gust, TC [1 ]
Zenke, M [1 ]
机构
[1] Univ Klinikum Aachen, Inst Biomed Engn, D-52074 Aachen, Germany
关键词
dendritic cells; immunotherapy; RNA;
D O I
10.1517/14712598.5.2.173
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];
摘要
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-transcluced 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-transcluced DCs as a therapeutic strategy in the treatment of cancer, as current studies on the treatment of infectious diseases are just beginning.
引用
收藏
页码:173 / 181
页数:9
相关论文
共 71 条
[1]
A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J].
Ambrosini, G ;
Adida, C ;
Altieri, DC .
NATURE MEDICINE, 1997, 3 (08) :917-921
[2]
Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors [J].
Ashley, DM ;
Faiola, B ;
Nair, S ;
Hale, LP ;
Bigner, DD ;
Gilboa, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (07) :1177-1182
[3]
Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[4]
Antibody response after vaccination with antigen-pulsed dendritic cells [J].
Battaini, F ;
Besusso, D ;
Sfondrini, L ;
Rossini, A ;
Morelli, D ;
Tagliabue, E ;
Menard, S ;
Balsari, A .
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, 2004, 19 (03) :213-220
[5]
Peptide-mediated RNA delivery: a novel approach for enhanced transfection of primary and post-mitotic cells [J].
Bettinger, T ;
Carlisle, RC ;
Read, ML ;
Ogris, M ;
Seymour, LW .
NUCLEIC ACIDS RESEARCH, 2001, 29 (18) :3882-3891
[6]
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo [J].
Boczkowski, D ;
Nair, SK ;
Snyder, D ;
Gilboa, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :465-472
[7]
Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules [J].
Bonehill, A ;
Heirman, C ;
Tuyaerts, S ;
Michiels, A ;
Breckpot, K ;
Brasseur, F ;
Zhang, Y ;
van der Bruggen, P ;
Thielemans, K .
JOURNAL OF IMMUNOLOGY, 2004, 172 (11) :6649-6657
[8]
Lentivirally transduced dendritic cells as a tool for cancer immunotherapy [J].
Breckpot, K ;
Dullaers, M ;
Bonehill, A ;
Van Meirvenne, S ;
Heirman, C ;
De Greef, C ;
van der Bruggen, P ;
Thielemans, K .
JOURNAL OF GENE MEDICINE, 2003, 5 (08) :654-667
[9]
Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells [J].
Brossart, P ;
Wirths, S ;
Stuhler, G ;
Reichardt, VL ;
Kanz, L ;
Brugger, W .
BLOOD, 2000, 96 (09) :3102-3108
[10]
Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer [J].
Caruso, DA ;
Orme, LM ;
Neale, AM ;
Radcliff, FJ ;
Amor, GM ;
Maixner, W ;
Downie, P ;
Hassall, TE ;
Tang, MLK ;
Ashley, DA .
NEURO-ONCOLOGY, 2004, 6 (03) :236-246