Gene-modified dendritic cells for use in tumor vaccines.
Dendritic cells (DCs) are potent antigen-presenting cells capable of priming activation of naive T cells. Because of their immunostimulatory capacity, immunization with DCs presenting tumor antigens has been proposed as a treatment regimen for cancer. The results from translational research studies and early clinical trials point to the need for improvement of DC-based tumor vaccines before they become a more broadly applicable treatment modality. In this regard, studies suggest that genetic modification of DCs to express tumor antigens and/or immunomodulatory proteins may improve their capacity to promote an antitumor response. Because the DC phenotype is relatively unstable, nonperturbing methods of gene transfer must be employed that do not compromise viability or immunostimulatory capacity. DCs expressing transgenes encoding tumor antigens have been shown to be more potent primers of antitumor immunity both in vitro and in animal models of disease; in some measures of immune priming, gene-modified DCs exceeded their soluble antigen-pulsed counterparts. Cytokine gene modification of DCs has improved their capacity to prime tumor antigen-specific T cell responses and promote antitumor immunity in vivo. Here, we review the current status of gene-modified DCs in both human and murine studies. Although successful results have been obtained to date in experimental systems, we discuss potential problems that have already arisen and may yet be encountered before gene-modified DCs are more widely applicable for use in human clinical trials.
Kirk
C J
CJ
Department of Surgery, Tumor Immunology Program of the Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor 48109-0666, USA. ckirk@umich.edu
Mulé
J J
JJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D004279:DNA, Viral