Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines

Richard C. Koya, Takahiro Kimura, Antoni Ribas, Nora Rozengurt, Gregory W. Lawson, Emmanuelle Faure-Kumar, He Jing Wang, Harvey Herschman, Noriyuki Kasahara, Renata Stripecke

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Approaches 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.

Original languageEnglish (US)
Pages (from-to)971-980
Number of pages10
JournalMolecular Therapy
Volume15
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines'. Together they form a unique fingerprint.

  • Cite this

    Koya, R. C., Kimura, T., Ribas, A., Rozengurt, N., Lawson, G. W., Faure-Kumar, E., Wang, H. J., Herschman, H., Kasahara, N., & Stripecke, R. (2007). Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines. Molecular Therapy, 15(5), 971-980. https://doi.org/10.1038/mt.sj.6300126