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Adenoviral-mediated transfer of human wild-type p53, GM-CSF and B7-1 genes results in growth suppression and autologous anti-tumor cytotoxicity of multiple myeloma cells in vitro

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Abstract

Multiple myeloma (MM) remains incurable despite the use of high-dose chemotherapy and stem cell transplantation. However, immunotherapy is expected to offer long-term disease control, or even possibly a cure. We have previously demonstrated the suppressive effect of a recombinant adenovirus carrying human wild-type p53, granulocyte–macrophage colony-stimulating factor, and B7-1 genes (Ad-p53/GM-CSF/B7-1) on the growth of laryngeal cancer cells. In the present study, we evaluated the effects of an Ad-p53/GM-CSF/B7-1-modified myeloma cell vaccine strategy aimed to induce apoptosis and to augment the immunogenicity of MM cells. Both MM cell lines and purified primary myeloma cells were infected with Ad-p53/GM-CSF/B7-1. High expression levels of these three genes were confirmed separately by Western blot, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. When wild-type p53, GM-CSF and B7-1 genes were introduced, the growth of MM cells was inhibited via enhanced apoptosis and the immunogenicity of tumor cells was augmented. The combinatorial effect of these three genes on inducing cytotoxic T lymphocytes (CTLs) was more evident than that of p53 individually or any combinations of two (p53 plus GM-CSF or p53 plus B7-1). Furthermore, significant proliferation of autologous peripheral blood lymphocytes (PBLs) and specific cytotoxicity against autologous primary MM cells were induced in vitro. These results suggest that myeloma cell vaccination co-transferred with p53, GM-CSF and B7-1 genes may be a promising immunotherapeutic approach against MM.

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Acknowledgements

This work was supported in part by grants from the Major State Basic Research Development Program of China (973 Program) (No. 2004CB518801 and No. 2002CB713804), the National High Technology Research and Development Program of China (863 Program) (No. 2003AA216050) and the National Science Foundation of China (No.30400189).

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  1. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, People’s Republic of China

    Su-Ping Ren, Chu-Tse Wu, Wen-Rong Huang, Zhuo-zhuang Lu, Xiang-Xu Jia, Lan Wang, Miao-Fen Lao & Li-Sheng Wang

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  1. Su-Ping Ren
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  2. Chu-Tse Wu
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  3. Wen-Rong Huang
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Correspondence to Li-Sheng Wang.

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Ren, SP., Wu, CT., Huang, WR. et al. Adenoviral-mediated transfer of human wild-type p53, GM-CSF and B7-1 genes results in growth suppression and autologous anti-tumor cytotoxicity of multiple myeloma cells in vitro. Cancer Immunol Immunother 55, 375–385 (2006). https://doi.org/10.1007/s00262-005-0011-z

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