Comparison of media and serum supplementation for generation of monophosphoryl lipid A/interferon-γ–matured type I dendritic cells for immunotherapy

Kolanowski, Sonja T.H.M.; Sritharan, Lathees; Lissenberg-Thunnissen, Suzanne N.; Schijndel, G. M. W. Van; Ham, S. Marieke van; Brinke, Anja ten

doi:10.1016/j.jcyt.2013.12.005

Cited by 15 publications

(9 citation statements)

References 28 publications

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“…It has described that ex-vivo DCs for clinical use are less immunogenic, because of a reduced expression of HLA and costimulatory molecules. Addition of human serum (autologous or pooled) to implement clinical grade DC performance appears to hamper cytokine production and reduce migratory capacity of DCs ( 37 , 38 ). Indeed, the high plasticity of DCs, that enable them to quickly sense in vivo stimuli , can become a critical point in formulating experimental protocols for ex-vivo DC cultures ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells

et al. 2018

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Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighboring cells as well as to cells in distant tissues. Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response. DCs are considered pivot cells of the immune system due to their exclusive ability to coordinate the innate and acquired immune responses, cross-present exogenous antigens, and prime naïve T cells. DCs are required for the induction and maintenance of long-lasting anti-tumor immunity and their exploitation has been extensively investigated for the design of anti-tumor vaccines. However, the clinical grade culture conditions that are required to generate DCs for therapeutic use can strongly affect their functions. Here, we investigated the immunomodulatory impact of MVs carrying the MUC1 tumor glycoantigen (MVsMUC1) as immunogen formulation on clinical grade DCs grown in X-VIVO 15 (X-DCs). Results indicated that X-DCs displayed reduced performance of the antigen processing machinery in term of diminished phagocytosis and acidification of the phagosomal compartment suggesting an altered immunogenicity of clinical grade DCs. Pulsing DCs with MVsMUC1 restored phagosomal alkalinization, triggering ROS increase. This was not observed when a soluble MUC1 protein was employed (rMUC1). Concurrently, MVsMUC1 internalization by X-DCs allowed MUC1 cross-processing. Most importantly, MVsMUC1 pulsed DCs activated IFNγ response mediated by MUC1 specific CD8+ T cells. These results strongly support the employment of tumor-derived MVs as immunogen platforms for the implementation of DC-based vaccines.

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Section: Discussionmentioning

confidence: 99%

Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells

et al. 2018

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“…A modified, less toxic version of LPS called 3-O-deacylated monophosphoryl lipid A (MPLA), which is derived from Salmonella minnesota R595, has been approved for use in human and is used in combination with Cervarix. MPLA matures DCs and together with IFNγ was demonstrated to produce high levels of IL-12 and induce CD8 + T cell responses in vitro [121]. A new synthetic TLR4 agonist, glucopyranosyl lipid A, has been used in combination with anti-DEC205 that targets HIV gag p24 to DCs in mouse studies.…”

Section: Maturation Of Dcsmentioning

confidence: 99%

Dendritic cell-based immunotherapy

2016

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Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity.

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“…Together with IFN-γ MPLA was demonstrated to produce high levels of IL-12 and induce CD8 + T cell responses in vitro. It was approved for use in humans and is used in combination with Cervarix (Kolanowski et al 2014). Lastly, small molecule synthetic TLR agonists can be effective adjuvants in anti-cancer vaccines.…”

Section: Structural Modificationmentioning

confidence: 99%

Plant-derived polysaccharides activate dendritic cell-based anti-cancer immunity

et al. 2018

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Today, cancers pose a major public health burden. Although a myriad of cancer treatments are available, only a few have achieved clinical efficacy. This is partly attributed to cancers capability to evade host immunity by converting dendritic cells (DCs) from potent stimulators to negative modulators of immunity. Dendritic cell-based immunotherapy attempts to resolve this problem by manipulating the functional characteristics of DCs. Plant-derived polysaccharides (PDPs) can stimulate the maturation of DCs conferring on them the capacity to present internalised tumorigenic antigens to naïve T cells and subsequently priming T cells to eliminate tumours. PDPs have been used as immune modulators and later as anti-cancer agents by Traditional Chinese Medicine practitioners for centuries. They are abundant in nature and form a large group of heterogeneous though structurally related macromolecules that exhibit diverse immunological properties. They can induce antigen pulsed DCs to acquire functional characteristics in vitro which can subsequently be re-introduced into cancer patients. They can also be used as adjuvants in DC-based vaccines or independently for their intrinsic anti-tumour activities. Clinically, some in vitro generated DCs have been shown to be both safe and immunogenic although their clinical application is limited in part by unsatisfactory functional maturation as well as impaired migration to draining lymph nodes where T cells reside. We review the relative potencies of individual PDPs to induce both phenotypic and functional maturation in DCs, their relative abilities to activate anti-cancer immunity, the possible mechanisms by which they act and also the challenges surrounding their clinical application.

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Comparison of media and serum supplementation for generation of monophosphoryl lipid A/interferon-γ–matured type I dendritic cells for immunotherapy

Cited by 15 publications

References 28 publications

Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells

Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells

Dendritic cell-based immunotherapy

Plant-derived polysaccharides activate dendritic cell-based anti-cancer immunity

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