Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

Redas Trepiakas; Anders Elm Pedersen; Ozcan Met; Morten H Hansen; Annika Berntsen; Inge Marie Svane

doi:10.1016/j.vaccine.2008.03.054

Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

Redas Trepiakas, Anders Elm Pedersen, Ozcan Met, Morten H Hansen, Annika Berntsen, Inge Marie Svane

Department of Immunology and Microbiology

28 Citations (Scopus)

Abstract

The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.

Original language	English
Journal	Vaccine
Volume	26
Issue number	23
Pages (from-to)	2824-32
Number of pages	8
ISSN	0264-410X
DOIs	https://doi.org/10.1016/j.vaccine.2008.03.054
Publication status	Published - 2008

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Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients. / Trepiakas, Redas; Pedersen, Anders Elm ; Met, Ozcan et al.

In: Vaccine, Vol. 26, No. 23, 2008, p. 2824-32.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.",

abstract = "The current {"}gold standard{"} for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.",

author = "Redas Trepiakas and Pedersen, {Anders Elm} and Ozcan Met and Hansen, {Morten H} and Annika Berntsen and Svane, {Inge Marie}",

note = "Keywords: Cancer Vaccines; Cytokines; Dendritic Cells; Electroporation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Kinetics; Lymphocyte Culture Test, Mixed; Monocytes; Neoplasms; RNA, Messenger; Receptors, CCR7; T-Lymphocytes",

year = "2008",

doi = "10.1016/j.vaccine.2008.03.054",

language = "English",

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T1 - Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

AU - Trepiakas, Redas

AU - Pedersen, Anders Elm

AU - Met, Ozcan

AU - Hansen, Morten H

AU - Berntsen, Annika

AU - Svane, Inge Marie

N1 - Keywords: Cancer Vaccines; Cytokines; Dendritic Cells; Electroporation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Kinetics; Lymphocyte Culture Test, Mixed; Monocytes; Neoplasms; RNA, Messenger; Receptors, CCR7; T-Lymphocytes

PY - 2008

Y1 - 2008

N2 - The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.

AB - The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.

U2 - 10.1016/j.vaccine.2008.03.054

DO - 10.1016/j.vaccine.2008.03.054

M3 - Journal article

C2 - 18450338

SN - 0264-410X

VL - 26

SP - 2824

EP - 2832

JO - Vaccine

JF - Vaccine

IS - 23

ER -

Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

Abstract

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