Molecular Biology

, Volume 52, Issue 2, pp 222–231 | Cite as

Maturation and Antigen Loading Protocols Influence Activity of Anticancer Dendritic Cells

Molecular Cell Biology
  • 4 Downloads

Abstract

The practical use of dendritic cell-based vaccines in anticancer therapy is limited by a lack of standards for dendritic cell (DC) generation, as well as standard procedures for controlling their activation and the technique of DC loading with nucleic acids encoding tumor antigens. Analyzing the currently available data, the most promising cocktails for DC maturation were selected and a comparative study of the cocktails and time of maturation on the capacity of DC to activate T-cell immune response has been performed. A study of the expression of surface markers and the production of IL-12, IL-6, and IL-10 cytokines, as well as the efficacy of T-cell activation showed that the use of the standard 7-day maturation protocol is preferable to the 4-day maturation protocol. Cocktails composed of TNF-α, IL-1β, IFN-α, IFN-γ, and poly(I:C), as well as TNF-α, IL-1β, IFN-γ, R848, and PGE2 were shown to be the most efficient activators of DCs. A comparison of the efficacy of different methods of DNA transfection into DCs and RNA delivery using alphavirus vectors demonstrated the superiority of magnet-assisted transfection (MATra) to other protocols.

Keywords

dendritic cells antigen delivery cytotoxic T lymphocytes anticancer immunotherapy 

Abbreviations

DC

dendritic cells

CD

cluster of differentiation

IL

interleukin

TNF-α

tumor necrosis factor α

IFN-α

interferon α

PGE2

prostaglandin E2

GM-CSF

granulocyte-macrophage colony-stimulating factor

MHC

major histocompatibility complex

SFV

Semliki forest virus

Sin

Sindbis virus

LPS

lipopolysaccharide

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Skalova K., Mollova K., Michalek J. 2010. Human myeloid dendritic cells for cancer therapy: Does maturation matter? Vaccine. 28, 5153–5160.CrossRefPubMedGoogle Scholar
  2. 2.
    Schuler G. 2010. Dendritic cells in cancer immunotherapy. Eur. J. Immunol. 40, 2123–2130.CrossRefPubMedGoogle Scholar
  3. 3.
    Nazarkina Zh.K., Laktionov P.P. 2015. Preparation of dendritic cells for cancer immunotherapy. Biochemistry (Moscow). Suppl. Ser. B: Biomed. Chem. 8, 85–93.CrossRefGoogle Scholar
  4. 4.
    Maksyutov A.Z., Lopatnikova Y.A., Kurilin V.V., et al. 2014. Efficiency studies of induced cytotoxic immune response of mononuclear cells by means of dendritic cells transfected by polyepitopic HER2/ErbB2 constructs. Med. Immunol. (Russia). 16, 417–424.CrossRefGoogle Scholar
  5. 5.
    Nehaeva T.L., Baldueva I.A., Novik A.V., et al. 2014. Development and optimization of vaccines based on autologous dendritic cells (DC) is activated by cancertestis antigens for the treatment of patients with skin melanoma. J. Ural Med. Acad. Sci. 5, 92–98.Google Scholar
  6. 6.
    Morse M.A., Zhou L.J., Tedder T.F., et al. 1997. Generation of dendritic cells in vitro from peripheral blood mononuclear cells with granulocyte-macrophage-colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha for use in cancer immunotherapy. Ann. Surg. 226, 6–16.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zobywalski A., Javorovic M., Frankenberger B., et al. 2007. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70. J. Transl. Med. 5,18.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Dohnal A.M., Witt V., Hügel H., et al. 2007. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy, 9, 755–770.CrossRefPubMedGoogle Scholar
  9. 9.
    Mailliard R.B., Wankowicz-Kalinska A., Cai Q., et al. 2004. alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res. 64, 5934–5937.CrossRefPubMedGoogle Scholar
  10. 10.
    Obermaier B., Dauer M., Herten J., et al. 2003. Development of a new protocol for 2-day generation of mature dendritic cells from human monocytes. Biol. Proceed. Online. 5, 197–203.CrossRefGoogle Scholar
  11. 11.
    Bürdek M., Spranger S., Wilde S., et al. 2010. Three-day dendritic cells for vaccine development: Antigen uptake, processing and presentation. J. Transl. Med. 28 (8),90.CrossRefGoogle Scholar
  12. 12.
    Bol K.F., Schreibelt G., Gerritsen W.R., et al. 2016. Dendritic cell-based immunotherapy: State of the art and beyond. Clin. Cancer Res. 22, 1897–1906.CrossRefPubMedGoogle Scholar
  13. 13.
    Wheeler C.J., Black K.L. 2009. DCVax-Brain and DC vaccines in the treatment of GBM. Expert Opin. Investig. Drugs. 18, 509–519.CrossRefPubMedGoogle Scholar
  14. 14.
    Yamanaka R., Homma J., Yajima N. 2005. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin. Cancer Res. 11, 4160–4167.CrossRefPubMedGoogle Scholar
  15. 15.
    Javed A., Sato S., Sato T. 2016. Autologous melanoma cell vaccine using monocyte-derived dendritic cells (NBS20/eltrapuldencel-T). Future Oncol. 12, 751–762.CrossRefPubMedGoogle Scholar
  16. 16.
    Schadendorf D., Ugurel S., Schuler-Thurner B. 2006. Dacarbazine (DTIC. versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: A randomized Phase III trial of the DC study group of the DeCOG. Ann. Oncol. 17, 563–570.Google Scholar
  17. 17.
    Vasilevska J., Skrastina D., Spunde K., et al. 2012. Semliki Forest virus biodistribution in tumor-free and 4T1 mammary tumor-bearing mice: A comparison of transgene delivery by recombinant virus particles and naked RNA replicon. Cancer Gene Therapy J. 19, 579–587.CrossRefGoogle Scholar
  18. 18.
    Zajakina A., Vasilevska J., Zhulenkov D., et al. 2014. High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in mouse mammary tumor model. BMC Cancer. 20(14),460.CrossRefGoogle Scholar
  19. 19.
    Liljestrom P., Garoff H. 1991. A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (NY). 9, 1356–1361.CrossRefGoogle Scholar
  20. 20.
    Bredenbeek P.J., Frolov I., Rice C.M., et al. 1993. Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs. J. Virol. 67, 6439–6446.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Vopenkova K., Mollova K., Buresova I., et al. 2012. Complex evaluation of human monocyte-derived dendritic cells for cancer immunotherapy. J. Cell Mol. Med. 16, 2827–2837.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lundstrom K. 2015. Alphaviruses in gene therapy. Viruses. 7, 2321–2333.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Colombo M.P., Trinchieri G. 2002. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 13, 155–168.CrossRefPubMedGoogle Scholar
  24. 24.
    Rincón M., Anguita J., Nakamura T., et al. 1997. Interleukin( IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J. Exp. Med., 185, 461–469.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hunter C.A., Jones S.A. 2015. IL-6 as a keystone cytokine in health and disease. Nat. Immunol. 16, 448–457.CrossRefPubMedGoogle Scholar
  26. 26.
    Fujimoto M., Nakano M., Terabe F., et al. 2011. The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells. J. Immunol. 186, 32–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Moran T.P., Collier M., McKinnon K.P., et al. 2005. A novel viral system for generating antigen-specific T cells. J. Immunol. 175, 3431–3438.CrossRefPubMedGoogle Scholar
  28. 28.
    Morse M.A., Coleman R.E., Akabani G., et al. 1999. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res. 59, 56–58.PubMedGoogle Scholar
  29. 29.
    Mempel T.R., Henrickson S.E., von Andrian U.H. 2004. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature. 427, 154–159.CrossRefPubMedGoogle Scholar
  30. 30.
    Hugues S., Fetler L., Bonifaz L., et al. 2004. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat. Immunol. 5, 1235–1242.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • Zh. K. Nazarkina
    • 1
    • 2
  • A. Zajakina
    • 3
  • P. P. Laktionov
    • 1
    • 2
  1. 1.Institute of Chemical Biology and Fundamental Medicine, Siberian BranchRussian Academy of SciencesNovosibirskRussia
  2. 2.Meshalkin National Medical Research CenterMinistry of Health of the Russian FederationNovosibirskRussia
  3. 3.Latvian Biomedical Research and Study CentreRigaLatvia

Personalised recommendations