Use of Dendritic Cell Receptors as Targets for Enhancing Anti-Cancer Immune Responses

Hossain, Kamal; Wall, Kathleen

doi:10.3390/cancers11030418

Cited by 71 publications

(59 citation statements)

References 120 publications

(122 reference statements)

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“…In another study, cell-specific delivery of FLuc and IL-10 mRNA to leukocytes (Ly6c+) was achieved by coating the formulated mRNA-containing LNPs with anti-L6c+ monoclonal antibodies [178]. Alternatively, DCs and macrophages express receptors with the ability to present antigens, e.g., C-type lectin receptors [179], which recognize sugar groups such as mannoseand fucose-terminated glycans [180] and mediate the endocytosis of mannose-modified nanoparticles. This has been exploited for transfection of GFP mRNA into DCs by self-assembly of mannose-cholesterol conjugates with varying PEG units as linkers [181].…”

Section: Cell-specific Mrna Deliverymentioning

confidence: 99%

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

et al. 2020

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In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.

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Section: Cell-specific Mrna Deliverymentioning

confidence: 99%

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

et al. 2020

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“…Recently, phenotypes and properties of tumor-associated DCs have been extensively studied. DCs isolated from several tumor models and cancer patients were found to possess tolerogenic properties, such as low levels of co-stimulatory molecules (CD80, CD86) and low production of Th1-polarizing cytokine IL-12 [ 18 , 36 , 37 ]. Notably, we observed similar results in our in vivo experiment ( Figure 5 C).…”

Section: Discussionmentioning

confidence: 99%

“…Here, we investigated the immunomodulatory effect of Ocs-P in innate and adaptive immunity on the basis of dendritic cells (DCs), which are critical for initiating the adaptive immune response [18], and explored the major mechanisms controlling DC maturation. Additionally, immunological functions of Ocs-P as a potent immunostimulator that induces strong anticancer immunity were investigated.…”

Section: Introductionmentioning

confidence: 99%

Edible Oxya chinensis sinuosa—Derived Protein as a Potential Nutraceutical for Anticancer Immunity Improvement

et al. 2020

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Oxya chinensis sinuosa (Ocs) is consumed as representative edible insects in Asia, but its function in various immune systems remains unclear. This study aimed to demonstrate the immunomodulatory effect, particularly on the innate and adaptive immune response, of Ocs protein (Ocs-P) and to investigate its function as a potent anticancer immunostimulant when administered during the progression stage of colon carcinoma in tumor-bearing mice. Our in vitro results demonstrated that Ocs-P treatment induces phenotypic alteration (increased expression of surface molecules and production of Th1-polarizing cytokines and decreased antigen uptake ability) of dendritic cells (DCs) through the activation of MAPK and NF-κB-dependent signaling pathways. Additionally, Ocs-P-stimulated DCs initiated differentiation of naive T cells into IFN-γ-producing Th1-type T cells effectively and activated cytotoxic CD8+ T cell response. In colon carcinoma-bearing mouse models, oral administration of Ocs-P inhibited tumor growth and restored the expression of decreased surface molecules in lineage-CD11c+MHC-II+ splenic DCs. Furthermore, Ocs-P administration enhanced the generation of multifunctional CD4+ and CD8+ T cells expressing Th1-type cytokines (TNF-α, IFN-γ, and IL-2) and the degranulation marker (CD107a). Collectively, these results suggest that Ocs-P demonstrates an immunostimulatory effect and may induce powerful anticancer immunity.

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“…It is a type 2, mannose-specific C-type lectin that also works as a cytosolic DNA-sensor. It induces specific immune responses upon the recognition of glycans through its carbohydrate recognition domains (CRD) [16,17]. After DC-SIGN recognizes fucose-based PAMPs, it activates IKKε.…”

Section: C-type Lectin Receptors (Clrs)mentioning

confidence: 99%

Dendritic cell biology and its role in tumor immunotherapy

et al. 2020

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As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4 + and CD8 + T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DCbased tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.

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Use of Dendritic Cell Receptors as Targets for Enhancing Anti-Cancer Immune Responses

Cited by 71 publications

References 120 publications

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

Edible Oxya chinensis sinuosa—Derived Protein as a Potential Nutraceutical for Anticancer Immunity Improvement

Dendritic cell biology and its role in tumor immunotherapy

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