Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Revisiting GM-CSF as an adjuvant for therapeutic vaccines

Cellular & Molecular Immunology volume 15, pages 187–189 (2018)Cite this article

Granulocyte macrophage colony stimulating factor (GM-CSF) is generally considered to be a proinflammatory cytokine; GM-CSF-based vaccines have been shown to elicit potent antitumor and antiviral immune responses in preclinical experiments. In clinical trials, however, these effects were not as robust and sometimes even contradicted the findings from animal models. In this commentary, we aim to discuss the latest advances in this field, hoping that an upto-date and comprehensive understanding of this molecule will help others design effective GM-CSF-based strategies for antiviral and anticancer vaccines.

It is recognized that sufficient immunogenicity capable of breaking host immune tolerance is the key factor contributing to the efficacy of therapeutic vaccines against established tumors or persistent infections. To augment vaccines with lower immunogenicities, adjuvant incorporation has become an indispensable and widely adopted practice. To date, Alum, the first adjuvant licensed for human vaccines, remains in extended use. Newer alternatives, such as MPL, CpG and nano-emulsions with bacterial components/derivatives, are also effective in improving the immunogenicities of a multitude of vaccines.1 However, some of these regimens are not yet free of safety concerns; extensive clinical use of these adjuvants is therefore still some distance away. On the positive side, several cytokines, such as GM-CSF and IL-12, can evoke equally effective immune responses to vaccines.2 These originally lab-based findings are being actively tested in vivo to develop a new class of clinical immune enhancers. However, despite their repeated success in the laboratory, GM-CSF-adjuvant vaccines do not usually fare well in clinical tests. In fact, some GM-CSF-based preparations have been found to have effects in humans that contradict animal findings.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. O'Hagan DT, Fox CB . New generation adjuvants—from empiricism to rational design. Vaccine 2015; 33 (Suppl 2): B14–B20.

    Article  CAS  Google Scholar 

  2. Decker WK, Safdar A . Cytokine adjuvants for vaccine therapy of neoplastic and infectious disease. Cytokine Growth Factor Rev 2011; 22: 177–187.

    Article  CAS  Google Scholar 

  3. van de Laar L, Coffer PJ, Woltman AM . Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 2012; 119: 3383–3393.

    Article  CAS  Google Scholar 

  4. Zhu YT, Zhao Z, Fu XY, Luo Y, Lei CY, Chen W et al. The granulocyte macrophage-colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer. Stem Cell Res 2014; 13: 111–122.

    Article  CAS  Google Scholar 

  5. Chen G, Gupta R, Petrik S, Laiko M, Leatherman JM, Asquith JM et al. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. Cancer Immunol Res 2014; 2: 949–961.

    Article  CAS  Google Scholar 

  6. Ohno S, Okuyama R, Aruga A, Sugiyama H, Yamamoto M . Phase I trial of Wilms' Tumor 1 (WT1) peptide vaccine with GM-CSF or CpG in patients with solid malignancy. Anticancer Res 2012; 32: 2263–2269.

    CAS  PubMed  Google Scholar 

  7. Mitchell DA, Sayour EJ, Reap E, Schmittling R, DeLeon G, Norberg P et al. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. Cancer Immunol Res 2015; 3: 320–325.

    Article  CAS  Google Scholar 

  8. Spearman P, Kalams S, Elizaga M, Metch B, Chiu YL, Allen M et al. Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial. Vaccine 2009; 27: 243–249.

    Article  CAS  Google Scholar 

  9. Lassi K, Dawson NA . Update on castrate-resistant prostate cancer: 2010. Curr Opin Oncol 2010; 22: 263–267.

    Article  Google Scholar 

  10. Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I . High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 2004; 64: 6337–6343.

    Article  CAS  Google Scholar 

  11. Parmiani G, Castelli C, Pilla L, Santinami M, Colombo MP, Rivoltini L . Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. Ann Oncol 2007; 18: 226–232.

    Article  CAS  Google Scholar 

  12. Gaudreau S, Guindi C, Menard M, Benabdallah A, Dupuis G, Amrani A . GM-CSF induces bone marrow precursors of NOD mice to skew into tolerogenic dendritic cells that protect against diabetes. Cell Immunol 2010; 265: 31–36.

    Article  CAS  Google Scholar 

  13. Torres-Aguilar H, Aguilar-Ruiz SR, Gonzalez-Perez G, Munguia R, Bajana S, Meraz-Rios MA et al. Tolerogenic dendritic cells generated with different immunosuppressive cytokines induce antigen-specific anergy and regulatory properties in memory CD4+ T cells. J Immunol 2010; 184: 1765–1775.

    Article  CAS  Google Scholar 

  14. Wang X, Dong A, Xiao J, Zhou X, Mi H, Xu H et al. Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice. Cell Mol Immunol 2016; 13: 850–861.

    Article  CAS  Google Scholar 

  15. Zhao W, Zhou X, Zhao G, Lin Q, Wang X, Yu X et al. Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model. Hum Vaccin Immunother 2017 e-pub ahead of print 12 July 2017 doi:10.1080/21645515.2017.1344797.

    Article  Google Scholar 

Download references

Acknowledgements

This work is supported by grants from the National Science and Technology Major Program of Infectious Diseases (2012ZX10002002004-001, 2012ZX10004701 and 2013ZX10002001) and the Natural Science Foundation of China (31430027 and 81672016) to BW. We thank Dr Yan Shi for his critical review and suggestions and Dr Douglas Lowrie for his proofreading.

Author information

Author notes

  1. Weidong Zhao

    Present address: 2Current address: Department of Laboratory Medicine, Clinical Medicine College, Dali University, Dali 200032, China.,

Authors and Affiliations

  1. Key Laboratory of Medical Molecular Virology of the Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Weidong Zhao

  2. PhD, Key Laboratory of Medical Molecular Virology of the Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Shanghai, 200032, China

    Bin Wang

Authors
  1. Weidong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bin Wang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, W., Zhao, G. & Wang, B. Revisiting GM-CSF as an adjuvant for therapeutic vaccines. Cell Mol Immunol 15, 187–189 (2018). https://doi.org/10.1038/cmi.2017.105

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2017.105

This article is cited by

Search

Advanced search

Quick links