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Monophosphoryl lipid A plus IFNγ maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Dendritic cells (DCs) are promising antigen presenting cells for cancer treatment. Previously, we showed that the combination of monophosphoryl lipid A (MPLA) with IFNγ generates mature DCs that produce IL-12 and polarize CD4+ T cells towards a Th1 phenotype. Here, we extended these observations by showing that the DCs generated with the clinical grade maturation cocktail of MPLA/IFNγ induce superior tumour antigen-specific CD8+ CTL responses compared to the cytokine cocktail matured DCs that are currently used in the clinic. MPLA/IFNγ DCs can induce CTL responses in healthy individuals as well as in melanoma patients. The CTL induction was mainly dependent on the IL-12 produced by the MPLA/IFNγ DCs. The high amounts of induced CTLs are functional as they produce IFNγ and lyse target cells and this cytolytic activity is antigen specific and HLA restricted. Furthermore, the CTLs proved to kill tumour cells expressing endogenous tumour antigen in vitro. Therefore, MPLA/IFNγ DCs are very promising for the use in future cancer immunotherapy.

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Acknowledgments

We want to thank Miranda Dieker for performing the realtime PCR analysis.

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Authors and Affiliations

  1. Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, P.O. Box 9190, 1006 AD, Amsterdam, The Netherlands

    Anja ten Brinke, Gijs van Schijndel, Remco Visser & S. Marieke van Ham

  2. Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Jaap Jan Zwaginga

  3. Department of Immunohaematology-Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands

    Jaap Jan Zwaginga

  4. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

    Tanja D. de Gruijl

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  1. Anja ten Brinke
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Correspondence to Anja ten Brinke.

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ten Brinke, A., van Schijndel, G., Visser, R. et al. Monophosphoryl lipid A plus IFNγ maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential. Cancer Immunol Immunother 59, 1185–1195 (2010). https://doi.org/10.1007/s00262-010-0843-z

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  • DOI: https://doi.org/10.1007/s00262-010-0843-z

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