PMID- 10942374 OWN - NLM STAT- MEDLINE DCOM- 20000907 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 96 IP - 4 DP - 2000 Aug 15 TI - Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro. PG - 1327-33 AB - Dendritic cells (DCs) genetically modified to continually express and present antigens may be potent physiologic adjuvants for induction of prophylactic or therapeutic immunity. We have previously shown that an env and nef deleted HIV-1 vector (HIV-1 delta EN) pseudotyped with VSV-G transduced monocyte-derived macrophages as well as CD34(+) precursors of DCs. Here we extended these findings with HIV-1 delta EN to highly differentiated human DCs derived in culture from circulating monocytes (DCs). In addition, a new vector derived from HIV-1 delta EN but further deleted in its remaining accessory genes vif, vpr, and vpu (HIV-1 delta EN V(3)) was also tested. Both vectors efficiently transduced DCs. Transduction of DCs did not significantly alter their viability or their immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic potential of immature DCs, as well as their ability to differentiate into mature DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs transduced by the HIV-1 delta EN vector were able to elicit a primary antiviral cytotoxic T-cell response in autologous CD8 T cells. These results suggest that HIV-1-based vectors expressing viral antigens may be useful for in vivo active immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell therapy. (Blood. 2000;96:1327-1333) FAU - Gruber, A AU - Gruber A AD - Departments of Medicine and Biology, University of California, San Diego, CA, USA. FAU - Kan-Mitchell, J AU - Kan-Mitchell J FAU - Kuhen, K L AU - Kuhen KL FAU - Mukai, T AU - Mukai T FAU - Wong-Staal, F AU - Wong-Staal F LA - eng GR - AI44372/AI/NIAID NIH HHS/United States GR - AI45992/AI/NIAID 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 - Blood JT - Blood JID - 7603509 SB - IM MH - Acquired Immunodeficiency Syndrome/genetics/immunology/prevention & control MH - Antigen Presentation MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Cytotoxicity, Immunologic/*genetics MH - Dendritic Cells/*immunology MH - Gene Transfer Techniques MH - *Genetic Therapy MH - *Genetic Vectors MH - HIV-1/*genetics MH - Humans MH - Immunotherapy EDAT- 2000/08/15 11:00 MHDA- 2000/09/09 11:01 CRDT- 2000/08/15 11:00 PHST- 2000/08/15 11:00 [pubmed] PHST- 2000/09/09 11:01 [medline] PHST- 2000/08/15 11:00 [entrez] AID - S0006-4971(20)71946-4 [pii] PST - ppublish SO - Blood. 2000 Aug 15;96(4):1327-33.