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

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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 2007
Externally publishedYes

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Bone Marrow Cells
Dendritic Cells
Vaccines
Melanoma-Specific Antigens
Histocompatibility Antigens Class II
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Immunotherapy
Melanoma
Lymph Nodes
Clinical Trials
Antigens
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Koya, R. C., Kimura, T., Ribas, A., Rozengurt, N., Lawson, G. W., Faure-Kumar, E., ... 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

Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines. / Koya, Richard C.; Kimura, Takahiro; Ribas, Antoni; Rozengurt, Nora; Lawson, Gregory W.; Faure-Kumar, Emmanuelle; Wang, He Jing; Herschman, Harvey; Kasahara, Noriyuki; Stripecke, Renata.

In: Molecular Therapy, Vol. 15, No. 5, 05.2007, p. 971-980.

Research output: Contribution to journalArticle

Koya, RC, Kimura, T, Ribas, A, Rozengurt, N, Lawson, GW, Faure-Kumar, E, Wang, HJ, 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, vol. 15, no. 5, pp. 971-980. https://doi.org/10.1038/mt.sj.6300126
Koya, Richard C. ; Kimura, Takahiro ; Ribas, Antoni ; Rozengurt, Nora ; Lawson, Gregory W. ; Faure-Kumar, Emmanuelle ; Wang, He Jing ; Herschman, Harvey ; Kasahara, Noriyuki ; Stripecke, Renata. / Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines. In: Molecular Therapy. 2007 ; Vol. 15, No. 5. pp. 971-980.
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