Combination strategies to enhance the potency of monocyte-derived dendritic cell-based cancer vaccines

Fecek, Ronald J.; Storkus, Walter J.

doi:10.2217/imt-2016-0071

Cited by 10 publications

(6 citation statements)

References 87 publications

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“…Since chemotherapy in general was formerly considered immunosuppressive, little attention was given to the fact that this is not always true. Indeed, some drugs might potentiate the anti-tumor immune response, by inducing the now recognized “immunogenic cell death” (262, 263). However, due to the frequently observed cancer patients' DC dysfunctions, the simple immunogenic death may not be enough to disrupt the tumor-favoring status of the immune response in patients.…”

Section: Strategies To Improve the Clinical Effectiveness Of Mo-dc-bamentioning

confidence: 99%

Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy

et al. 2019

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Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.

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Section: Strategies To Improve the Clinical Effectiveness Of Mo-dc-bamentioning

confidence: 99%

Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy

et al. 2019

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“…Furthermore, chemotherapy can skew immunomodulatory cells in a more pro-inflammatory subset. Depletion of Tregs 12 and MDSCs 116 in the TME after chemotherapy treatment was already observed in preclinical and clinical studies 11, 12, 17, 23, 117, 118. Such immunological changes were even associated with clinical response 118, 119, 120, 121, 122.…”

Section: Main Textmentioning

confidence: 74%

“…The rather limited clinical efficacy of DC therapy can be dependent on DC therapy-related aspects, such as the choice of antigen, method of loading, or type of DCs used. Next to that, active immunosuppression by the tumor and the TME could also hamper the immune-activating potential of the administered DCs and suppress the function and infiltration of activated T cells 11, 12, 13…”

Section: Main Textmentioning

confidence: 99%

Enhancing Dendritic Cell Therapy in Solid Tumors with Immunomodulating Conventional Treatment

Belderbos

Aerts

Vroman

2019

Molecular Therapy - Oncolytics

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Dendritic cells (DCs) are the most potent antigen-presenting cells and are the key initiator of tumor-specific immune responses. These characteristics are exploited by DC therapy, where DCs are ex vivo loaded with tumor-associated antigens (TAAs) and used to induce tumor-specific immune responses. Unfortunately, clinical responses remain limited to a proportion of the patients. Tumor characteristics and the immunosuppressive tumor microenvironment (TME) of the tumor are likely hampering efficacy of DC therapy. Therefore, reducing the immunosuppressive TME by combining DC therapy with other treatments could be a promising strategy. Initially, conventional cancer therapies, such as chemotherapy and radiotherapy, were thought to specifically target cancerous cells. Recent insights indicate that these therapies additionally augment tumor immunity by targeting immunosuppressive cell subsets in the TME, inducing immunogenic cell death (ICD), or blocking inhibitory molecules. Therefore, combining DC therapy with registered therapies such as chemotherapy, radiotherapy, or checkpoint inhibitors could be a promising treatment strategy to improve the efficacy of DC therapy. In this review, we evaluate various clinical applicable combination strategies to improve the efficacy of DC therapy. Immunosuppressive Mechanisms of the TME and Tumor Cells that Hamper the Efficacy of DC Therapy Both tumor cells and immunosuppressive immune cells in the TME hamper the effectivity of DC therapy through various mechanisms, such as the expression of inhibitory molecules, secretion of inhibitory cytokines or enzymes, induction of tolerogenic cell death, and creation of a dense extracellular matrix. 18,19 Tumor cells recruit immunosuppressive immune cells, fibroblasts, 20 and endothelial cells to the TME through the secretion of growth factors, chemokines, and cytokines, thereby hampering the infiltration of DCs and other pro-inflammatory cells into the TME. 21,22 Moreover, fibroblasts and immunosuppresive immune cells interact synergistically with each other to maximize the immunosuppressive character of the TME.

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“…This approach entails the development of DC differentiation protocols, the choice of the antigens for DC loading, and the proper selection of adjuvants in the vaccine formulation. Although the relationship between ex vivo generated DCs and the different subsets of natural DCs is not fully elucidated [34][35][36], the availability of convenient, established protocols to expand and differentiate DCs from patient-derived monocytes (mo-DCs) has strongly supported the employment of mo-DCs in the majority of clinical trials [3,37]. Different protocols and cytokine cocktails can be used for differentiating mo-DCs in sufficient numbers for vaccination.…”

Section: Dc-based Vaccinesmentioning

confidence: 99%

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

et al. 2020

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The safety and feasibility of dendritic cell (DC)-based immunotherapies in cancer management have been well documented after more than twenty-five years of experimentation, and, by now, undeniably accepted. On the other hand, it is equally evident that DC-based vaccination as monotherapy did not achieve the clinical benefits that were predicted in a number of promising preclinical studies. The current availability of several immune modulatory and targeting approaches opens the way to many potential therapeutic combinations. In particular, the evidence that the immune-related effects that are elicited by immunogenic cell death (ICD)-inducing therapies are strictly associated with DC engagement and activation strongly support the combination of ICD-inducing and DC-based immunotherapies. In this review, we examine the data in recent studies employing tumor cells, killed through ICD induction, in the formulation of anticancer DC-based vaccines. In addition, we discuss the opportunity to combine pharmacologic or physical therapeutic approaches that can promote ICD in vivo with in situ DC vaccination.

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Combination strategies to enhance the potency of monocyte-derived dendritic cell-based cancer vaccines

Cited by 10 publications

References 87 publications

Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy

Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy

Enhancing Dendritic Cell Therapy in Solid Tumors with Immunomodulating Conventional Treatment

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

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