Genetically modified dendritic cells in cancer immunotherapy: a better tomorrow?
BACKGROUND
Dendritic cells (DC) are powerful antigen-presenting cells that induce and maintain primary cytotoxic T lymphocyte (CTL) responses directed against tumor antigens. Consequently, there has been much interest in their application as antitumor vaccines.


METHODS
A large number of DC-based vaccine trials targeting a variety of cancers have been conducted; however, the rate of reported clinically significant responses remains low. Modification of DC to express tumor antigens or immunostimulatory molecules through the transfer of genes or mRNA transfection offers a logical alternative with potential advantages over peptide- or protein antigen-loaded DC. In this article, we review the current results and future prospects for genetically modified DC vaccines for the treatment of cancer.


RESULTS
Genetically-modified dendritic cell-based vaccines represent a powerful tool for cancer therapy. Numerous preclinical and clinical studies have demonstrated the potential of dendritic cell vaccines alone or in combination with other therapeutic modalities.


CONCLUSIONS
Genetically modified DC-based anti-cancer vaccination holds promise, perhaps being best employed in the adjuvant setting with minimal residual disease after primary therapy, or in combination with other antitumor or immune-enhancing therapies.
Department of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Michael R
MR
Shurin
Melissa
M
Gregory
John C
JC
Morris
Anatoli M
AM
Malyguine
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012334:RNA, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D004274:DNA, Recombinant; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm