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CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma

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Abstract

Idiotype (Id) protein in combination with GM-CSF has been used as vaccines for immunotherapy of patients with myeloma and B-cell tumors and the results have been disappointing. To search for better immune adjuvants to improve the efficacy of Id-based immunotherapy in myeloma, we evaluated and compared the efficacy of vaccination of Id protein in combination with CpG or IFN-α, or GM-CSF as a control, in the 5TGM1 myeloma mouse model. Our results showed that Id vaccine combined with CpG or IFN-α, but not GM-CSF, not only efficiently protected mice from developing myeloma but also eradicated established myeloma. The therapeutic responses were associated with an induction of strong humoral immune responses including anti-Id antibodies, and cellular immune responses including Id- and myeloma-specific CD8+ cytotoxic T lymphocytes (CTLs), CD4+ type-1 T-helper (Th1) cells and memory T cells in mice receiving Id vaccine combined with CpG or IFN-α. Furthermore, Id vaccine combined with CpG or IFN-α induced Id- and tumor-specific memory immune responses that protected surviving mice from tumor rechallenge. Thus, our study clearly shows that CpG or IFN-α are better immune adjuvants than GM-CSF. This information will be important for improving the strategies of Id-based immunotherapy for patients with myeloma and other B-cell tumors.

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Abbreviations

GM-CSF:

Granulocyte-monocyte colony-stimulating factor

IFN-α:

Interferon-α

CpG:

Synthetic oligodeoxnucleotides containing unmethylated CG dinucleotides

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Acknowledgments

This study was supported by grants from the University of Texas M.D. Anderson Cancer Center, National Cancer Institute grants R01 s (CA96569, CA103978, CA138402, and CA138398) and P50 CA142509, the Leukemia and Lymphoma Society Translational Research Grants, Multiple Myeloma Research Foundation, and Commonwealth Foundation for Cancer Research.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0903, Houston, TX, 77030, USA

    Sungyoul Hong, Jianfei Qian, Haiyan Li, Jing Yang, Yong Lu, Yuhuan Zheng & Qing Yi

  2. Division of Cancer Medicine, and Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Sungyoul Hong, Jianfei Qian, Haiyan Li, Jing Yang, Yong Lu, Yuhuan Zheng & Qing Yi

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  1. Sungyoul Hong
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Correspondence to Qing Yi.

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Hong, S., Qian, J., Li, H. et al. CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma. Cancer Immunol Immunother 61, 561–571 (2012). https://doi.org/10.1007/s00262-011-1123-2

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