PMID- 10779157 OWN - NLM STAT- MEDLINE DCOM- 20000630 LR - 20071114 IS - 1043-0342 (Print) IS - 1043-0342 (Linking) VI - 11 IP - 6 DP - 2000 Apr 10 TI - Gene-modified dendritic cells for use in tumor vaccines. PG - 797-806 AB - 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. FAU - Kirk, C J AU - Kirk CJ AD - Department of Surgery, Tumor Immunology Program of the Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor 48109-0666, USA. ckirk@umich.edu FAU - Mule, J J AU - Mule JJ LA - eng GR - 1 R01 CA71669/CA/NCI NIH HHS/United States GR - 5 P01 CA59327/CA/NCI NIH HHS/United States GR - M01-RR00042/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PT - Review PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (DNA, Viral) SB - IM MH - Animals MH - Antigens, Neoplasm/genetics/metabolism MH - Cancer Vaccines/*genetics/immunology MH - Cytokines/genetics MH - DNA, Viral/genetics MH - *Dendritic Cells/cytology/metabolism MH - *Gene Transfer Techniques MH - Genetic Vectors MH - Humans MH - Mice RF - 68 EDAT- 2000/04/25 09:00 MHDA- 2000/07/08 11:00 CRDT- 2000/04/25 09:00 PHST- 2000/04/25 09:00 [pubmed] PHST- 2000/07/08 11:00 [medline] PHST- 2000/04/25 09:00 [entrez] AID - 10.1089/10430340050015419 [doi] PST - ppublish SO - Hum Gene Ther. 2000 Apr 10;11(6):797-806. doi: 10.1089/10430340050015419.