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Brinke, A. ten; Schijndel, G. van; Visser, R.; Gruijl, T.D. de; Zwaginga, J.J.; Ham, S.M. van (2010)

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

Article / Letter to editor
Dendritic cells (DCs) are promising antigen presenting cells for cancer treatment. Previously, we showed that the combination of monophosphoryl lipid A (MPLA) with IFN gamma 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/IFN gamma induce superior tumour antigen-specific CD8(+) CTL responses compared to the cytokine cocktail matured DCs that are currently used in the clinic. MPLA/IFN gamma 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/IFN gamma DCs. The high amounts of induced CTLs are functional as they produce IFN gamma 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....Show moreDendritic cells (DCs) are promising antigen presenting cells for cancer treatment. Previously, we showed that the combination of monophosphoryl lipid A (MPLA) with IFN gamma 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/IFN gamma induce superior tumour antigen-specific CD8(+) CTL responses compared to the cytokine cocktail matured DCs that are currently used in the clinic. MPLA/IFN gamma 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/IFN gamma DCs. The high amounts of induced CTLs are functional as they produce IFN gamma 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/IFN gamma DCs are very promising for the use in future cancer immunotherapy.Show less
Cytotoxic T lymphocyte Dendritic cells IL-12 Immunotherapy Monophosphoryl lipid A, MART-1 tumor-associated antigen serum-free conditions patients in-vitro effector function melanoma patients immune-responses memory interleukin-12 il-12 ctl
All authors
Brinke, A. ten; Schijndel, G. van; Visser, R.; Gruijl, T.D. de; Zwaginga, J.J.; Ham, S.M. van
Date
2010-08-31
Journal
Cancer Immunology, Immunotherapy
Volume
59
Issue
8
Pages
1185 - 1195
DOI
doi:10.1007/s00262-010-0843-z