Fusion hybrid of dendritic cells and engineered tumor cells expressing interleukin-12 induces type 1 immune responses against tumor.
OBJECTIVE
Dendritic cell (DC)-tumor fusion hybrid vaccinees that facilitate antigen presentation represent a novel powerful strategy in cancer immunotherapy. Preclinical studies have demonstrated that IL-12 promotes specific antitumor immunity mediated by T cells in several types of tumors. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between DCs and engineered J558/IL-12 myeloma cells secreting Th1 cytokine IL-12.


METHODS
The expression vector pcDNA-IL-12 was generated and transfected into J558 myeloma cells and then bone marrow-derived DCs were fused with engineered J558/IL-12 cells. The antitumor immunity derived from vaccination of the fusion hybrid DC/J558/IL-12 was evaluated in vitro and in vivo.


RESULTS
DC/J558/IL-12 cells secreted recombinant IL-12 (1.6 ng/mL), and inoculation of BALB/c mice with DC/J558/IL-12 hybrid induced a Th1 dominant immune response and resulted in tumor regression. Immunization of mice with engineered DC/J558/IL-12 hybrid elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro as well as more potent protective immunity against J558 tumor challenge in vivo than immunization with the mixture of DCs and J558/IL-12, J558/IL-12 and J558, respectively. Furthermore, the anti-tumor immunity mediated by DC/J558/IL-12 tumor cell vaccination in vivo appeared to be dependent on CD8+ CTL.


CONCLUSIONS
These results demonstrate that the engineered fusion hybrid vaccines that combine Th1 cytokine gene-modified tumor cells with DCs may be an attractive strategy for cancer immunotherapy.
Shi
Meiqing
M
Research Unit, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Su
Liping
L
Hao
Sigou
S
Guo
Xulin
X
Xiang
Jim
J
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells; D019496:Cancer Vaccines / Q000494:pharmacology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006822:Hybrid Cells / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection
D019496:Cancer Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12