Oncotarget

Research Papers:

Human DKK1 and human HSP70 fusion DNA vaccine induces an effective anti-tumor efficacy in murine multiple myeloma

Ting-Ting Liu _, Yang Wu and Ting Niu

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Oncotarget. 2018; 9:178-191. https://doi.org/10.18632/oncotarget.23352

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Abstract

Ting-Ting Liu1,2, Yang Wu3 and Ting Niu1

1 Department of Hematology & Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, P.R. China

2 Department of Internal Medicine, No. 4 West China Teaching Hospital, Sichuan University, Chengdu, P.R. China

3 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, P.R. China

Correspondence to:

Ting Niu, email:

Keywords: DKK1; hHSP70; fusion genetic vaccine; multiple myeloma; xenogeneic immunity

Received: January 02, 2017 Accepted: November 26, 2017 Published: December 17, 2017

Abstract

Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining. The side effects of vaccines were also monitored. We found that hDKK1-hHSP70 fusion vaccine could significantly inhibit tumor growth and prolonged the survival of the mice, whether prophylactic or therapeutic immunotherapy in vivo, by eliciting both humoral and cellular tumor-specific immune responses. A significant decrease of proliferation and increase of apoptosis were also observed in the tumor tissues injected with hDKK1-hHSP70 vaccine. These findings showed the xenogeneic homologous vaccination had stronger immunogenicity and minimal toxicity. Our study may provide an effective and safety immonutheraphy strategy for multiple myeloma.


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