PMID- 9334364 OWN - NLM STAT- MEDLINE DCOM- 19971121 LR - 20210102 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 186 IP - 8 DP - 1997 Oct 20 TI - Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity. PG - 1247-56 AB - Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen beta-galactosidase (betagal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing betagal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors. FAU - Song, W AU - Song W AD - Division of Pulmonary and Critical Care Medicine, The New York Hospital-Cornell Medical Center 10021, USA. FAU - Kong, H L AU - Kong HL FAU - Carpenter, H AU - Carpenter H FAU - Torii, H AU - Torii H FAU - Granstein, R AU - Granstein R FAU - Rafii, S AU - Rafii S FAU - Moore, M A AU - Moore MA FAU - Crystal, R G AU - Crystal RG LA - eng GR - K08-HL 02926/HL/NHLBI NIH HHS/United States GR - R01-AR 40667/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (DNA, Complementary) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - Adenocarcinoma/*immunology/prevention & control/therapy MH - Adenoviridae/*genetics/immunology MH - Animals MH - Bone Marrow Cells/immunology/virology MH - Bone Marrow Transplantation MH - Cell Line MH - Colonic Neoplasms/*immunology/prevention & control/therapy MH - DNA, Complementary/*immunology MH - Dendritic Cells/*immunology/*transplantation/virology MH - Gene Transfer Techniques MH - Genetic Vectors/immunology MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Lung Neoplasms/immunology/prevention & control/secondary MH - Lymphocyte Activation/genetics MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Models, Immunological MH - Neoplasm Transplantation MH - T-Lymphocytes, Cytotoxic/immunology MH - beta-Galactosidase/*immunology PMC - PMC2199096 EDAT- 1997/10/23 00:00 MHDA- 1997/10/23 00:01 PMCR- 1998/04/20 CRDT- 1997/10/23 00:00 PHST- 1997/10/23 00:00 [pubmed] PHST- 1997/10/23 00:01 [medline] PHST- 1997/10/23 00:00 [entrez] PHST- 1998/04/20 00:00 [pmc-release] AID - 10.1084/jem.186.8.1247 [doi] PST - ppublish SO - J Exp Med. 1997 Oct 20;186(8):1247-56. doi: 10.1084/jem.186.8.1247.