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

doi:10.1038/mt.sj.6300126

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	971-980
Number of pages	10
Journal	Molecular Therapy
Volume	15
Issue number	5
DOIs	https://doi.org/10.1038/mt.sj.6300126
State	Published - May 2007
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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10.1038/mt.sj.6300126

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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 journal › Article › peer-review

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

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.",

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

note = "Funding Information: We would like to thank Lily Wu{\textquoteright}s (UCLA) group and David Stout (UCLA) for assistance with the imaging analyses, Robert Prins (UCLA) for technical assistance regarding TRP2 specific immune responses, and Michael Roth (UCLA) for support and critical reading of this manuscript. This work was supported by grants from the Margareth E. Early Research Trust and Stop Cancer (to R.S.), the CURE/Digestive Diseases Research Center Gene Transfer Core (NIH, 2P30DK041301), the UCLA Mouse Pathology Core, the UCLA Flow Cytometry Core, and the UCLA Center for In Vivo Imaging in Cancer Biology (NIH 2P50CA086306-06). R.C.K. was supported by a UCLA/Jonsson Comprehensive Cancer Center postdoctoral fellowship.",

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AU - Lawson, Gregory W.

AU - Faure-Kumar, Emmanuelle

AU - Wang, He Jing

AU - Herschman, Harvey

AU - Kasahara, Noriyuki

AU - Stripecke, Renata

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N2 - 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.

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

Abstract

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