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 | |
| State | Published - May 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
Cite this
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
}
TY - JOUR
T1 - Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines
AU - Koya, Richard C.
AU - Kimura, Takahiro
AU - Ribas, Antoni
AU - Rozengurt, Nora
AU - Lawson, Gregory W.
AU - Faure-Kumar, Emmanuelle
AU - Wang, He Jing
AU - Herschman, Harvey
AU - Kasahara, Noriyuki
AU - Stripecke, Renata
PY - 2007/5
Y1 - 2007/5
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=34247189774&partnerID=8YFLogxK
U2 - 10.1038/mt.sj.6300126
DO - 10.1038/mt.sj.6300126
M3 - Article
C2 - 17375074
AN - SCOPUS:34247189774
VL - 15
SP - 971
EP - 980
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 5
ER -