Immune Netw.  2006 Sep;6(3):154-162. 10.4110/in.2006.6.3.154.

Anti-cancer Effect of Hematopoietic Stem Cell-derived Allogeneic-DC Vaccine in Melanoma Metastasis Model

• Kim MJ
• Shon HJ
• Baek S
• Lee KE
• Lee YJ
• Lee H

• KMID: 1808160
• DOI: http://doi.org/10.4110/in.2006.6.3.154

Abstract

BACKGROUND: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model.
METHODS
B16F10 melanoma cells (5 x 10(4)/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval.
RESULTS
Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: 2.667+/-0.184, 2.500+/-0.463, 2.000+/-0.286, 1.500+/-0.286, 1.667+/-0.297 for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-gamma secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate (2,643.3+/-5,89.7, 8,561.5+/-2,204.9. 6,901.2+/-141.1 pg/1 x 10(6) cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity.
CONCLUSION
Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

Keyword

Stem cell-derived DC; allogeneic DC; anti-cancer immunotherapy

MeSH Terms

Animals
Bone Marrow
Dendritic Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunotherapy
Interleukin-4
Killer Cells, Natural
Leukapheresis
Melanoma*
Mice
Neoplasm Metastasis*
Stem Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4