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- Title
Lentiviral Vector–mediated Autonomous Differentiation of Mouse Bone Marrow Cells into Immunologically Potent Dendritic Cell Vaccines.
- Authors
Koya, Richard C.; Kimura, Takahiro; Ribas, Antoni; Rozengurt, Nora; Lawson, Gregory W.; Faure-Kumar, Emmanuelle; He-jing Wang; Herschman, Harvey; Kasahara, Noriyuki; Stripecke, Renata
- Abstract
See page 846Approaches facilitating generation of dendritic cell (DC) vaccines for clinical trials and enhancing their viability, bio-distribution, and capacity to stimulate antigen-specific immune responses are critical for immunotherapy. We programmed mouse bone marrow (BM) cells with lentiviral vectors (LV-GI4) so that they produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in an autonomous manner. DC/LV-GI4 cells underwent autonomous trans-differentiation to yield typical phenotypic characteristics of DCs. DC/LV-GI4 cells that self-differentiated either ex vivo or in vivo showed persistent and robust viability and stimulated high influx of DCs into draining lymph nodes (LNs). The immunostimulatory efficacy of DC/LV-GI4 cells was evaluated using MART1 and TRP2 as co-expressed melanoma antigens. Mice vaccinated with DC/LV-GI4 cells that self-differentiated in vitro or in vivo produced potent antigen-specific responses against melanoma, which correlated with protective and long-term therapeutic anti-tumor effects. Thus, DC precursors can be genetically engineered after a single ex vivo manipulation, resulting in DC vaccines with improved activity.Molecular Therapy (2007) 15 5, 971–980. doi:10.1038/mt.sj.6300126
- Subjects
DENDRITIC cells; VIRUS diseases; IMMUNE response; CELLULAR immunity; GENETIC transformation; GENETIC engineering; THERAPEUTICS; GENE therapy
- Publication
Molecular Therapy, 2007, Vol 15, Issue 5, p971
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.sj.6300126