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01-08-2010 | Original Article

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

Authors: Anja ten Brinke, Gijs van Schijndel, Remco Visser, Tanja D. de Gruijl, Jaap Jan Zwaginga, S. Marieke van Ham

Published in: Cancer Immunology, Immunotherapy | Issue 8/2010

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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Title: Monophosphoryl lipid A plus IFNγ maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential
Authors: Anja ten Brinke
Gijs van Schijndel
Remco Visser
Tanja D. de Gruijl
Jaap Jan Zwaginga
S. Marieke van Ham
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0843-z

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