RNA-loaded dendritic cells: more than a tour de force in cancer therapeutics

Immunotherapy ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1129-1147
Author(s):  
Aishwarya Joshi ◽  
Nikunj Tandel ◽  
Priyanka Tyagi ◽  
Sarat K Dalai ◽  
Prakash S Bisen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Conventional Treatment ◽  
Treatment Options ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Vital Role ◽  
Delivery Vehicles ◽  
Immune Competency ◽  
Potential Use

A wide array of therapeutic strategies has been implemented against cancers, yet their clinical benefit is limited. The lack of clinical efficacy of the conventional treatment options might be due to the inept immune competency of the patients. Dendritic cells (DCs) have a vital role in initiating and directing immune responses and have been frequently used as delivery vehicles in clinical research. The recent clinical data suggest the potential use of DCs pulsed with nucleic acid, especially with RNA holds a great potential as an immunotherapeutic measure with compare to other cancer therapeutics. This review mainly deals with the DCs and their role in transfection with RNA in cancer immunotherapy.

scholarly journals Immunological and Toxicological Considerations for the Design of Liposomes

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 190 ◽  
Author(s):  
Collin T. Inglut ◽  
Aaron J. Sorrin ◽  
Thilinie Kuruppu ◽  
Shruti Vig ◽  
Julia Cicalo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasma Proteins ◽  
Cancer Therapeutics ◽  
Mononuclear Phagocyte ◽  
Clinical Use ◽  
Physiochemical Properties ◽  
Drug Delivery Vehicles ◽  
Liposomal Formulations ◽  
Delivery Vehicles ◽  
Shed Light

Liposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from the encapsulated therapeutic agent. Decades of research have been dedicated to studying and optimizing liposomal formulations for a variety of medical applications, ranging from cancer therapeutics to analgesics. Some effort has also been made to elucidate the toxicities and immune responses that these drug formulations may elicit. Notably, intravenously injected liposomes can interact with plasma proteins, leading to opsonization, thereby altering the healthy cells they come into contact with during circulation and removal. Additionally, due to the pharmacokinetics of liposomes in circulation, drugs can end up sequestered in organs of the mononuclear phagocyte system, affecting liver and spleen function. Importantly, liposomal agents can also stimulate or suppress the immune system depending on their physiochemical properties, such as size, lipid composition, pegylation, and surface charge. Despite the surge in the clinical use of liposomal agents since 1995, there are still several drawbacks that limit their range of applications. This review presents a focused analysis of these limitations, with an emphasis on toxicity to healthy tissues and unfavorable immune responses, to shed light on key considerations that should be factored into the design and clinical use of liposomal formulations.

scholarly journals The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Reza Hosseini ◽  
Leila Asef-Kabiri ◽  
Hassan Yousefi ◽  
Hamzeh Sarvnaz ◽  
Majid Salehi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Treatment Options ◽  
Vaccination Strategy ◽  
Therapeutic Approaches ◽  
Therapeutic Level ◽  
Tumor Exosomes ◽  
And Function ◽  
Insight Into ◽  
Dominant Influence

AbstractTumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections. We also briefly describe the importance of TDEs at therapeutic level to help guide future treatment options, in particular DC-based vaccination strategy, and review advances in the design and discovery of exosome inhibitors. Understanding the exosomal content and the pathways by which TDEs are responsible for immune evasion may help to revise treatment rationales and devise novel therapeutic approaches to overcome the hurdles in cancer treatment.

Influenza mimetic protein–polymer nanoparticles as antigen delivery vehicles to dendritic cells for cancer immunotherapy

Nanoscale ◽  
2019 ◽  
Vol 11 (29) ◽  
pp. 13878-13884 ◽  
Author(s):  
Chaeyeon Lee ◽  
Leeja Jose ◽  
KyuHwan Shim ◽  
Seong Soo A. An ◽  
Sunah Jang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Antigen ◽  
Polymer Nanoparticles ◽  
Antigen Delivery ◽  
Protein Polymer ◽  
Delivery Vehicles

We introduce virus-mimetic polymer nanoparticles as tumor antigen delivery vehicles to induce adjuvant-free cancer Ag specific-immune responses.

scholarly journals Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 433
Author(s):  
Valeria Lucarini ◽  
Ombretta Melaiu ◽  
Patrizia Tempora ◽  
Silvia D’Amico ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Prognostic Significance ◽  
Therapeutic Strategies ◽  
T Cell Infiltration ◽  
Experimental Mouse ◽  
New Strategies

Tumor-infiltrating CD8+ T cells have been shown to play a crucial role in controlling tumor progression. However, the recruitment and activation of these immune cells at the tumor site are strictly dependent on several factors, including the presence of dendritic cells (DCs), the main orchestrators of the antitumor immune responses. Among the various DC subsets, the role of cDC1s has been demonstrated in several preclinical experimental mouse models. In addition, the high density of tumor-infiltrating cDC1s has been associated with improved survival in many cancer patients. The ability of cDC1s to modulate antitumor activity depends on their interaction with other immune populations, such as NK cells. This evidence has led to the development of new strategies aimed at increasing the abundance and activity of cDC1s in tumors, thus providing attractive new avenues to enhance antitumor immunity for both established and novel anticancer immunotherapies. In this review, we provide an overview of the various subsets of DCs, focusing in particular on the role of cDC1s, their ability to interact with other intratumoral immune cells, and their prognostic significance on solid tumors. Finally, we outline key therapeutic strategies that promote the immunogenic functions of DCs in cancer immunotherapy.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein - Protein Interactions in Cancer: Mechanistic View

2019 ◽  
Vol 19 (6) ◽  
pp. 430-448 ◽  
Author(s):  
Khalid Bashir Dar ◽  
Aashiq Hussain Bhat ◽  
Shajrul Amin ◽  
Syed Anjum ◽  
Bilal Ahmad Reshi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Throughput Screening ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Adaptor Proteins ◽  
Therapeutic Strategies ◽  
Small Gtpases ◽  
Beta Catenin ◽  
Protein Protein Interactions ◽  
Apoptosis Protein

Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer. This review explores the candidature of various proteins involved in cellular trafficking (small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc), signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family), which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T Cell Factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/ drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high throughput screening (HTS) and fragment-based technology could play an imperative role in designing cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence, protein sequence/structure and domain data could serve as competent tools for predicting PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics, genomics, biochemistry, and molecular dynamics for successful treatment of cancer.

scholarly journals Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Melanie R. Neeland ◽  
Samantha Bannister ◽  
Vanessa Clifford ◽  
Kate Dohle ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Phase ◽  
Innate Immune ◽  
Low Density ◽  
Innate Immune Responses ◽  
Immunological Mechanisms ◽  
Activated Neutrophils ◽  
Classical Monocytes

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

scholarly journals A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

2021 ◽  
Vol 22 (3) ◽  
pp. 1118
Author(s):  
Abdulaziz Alamri ◽  
Derek Fisk ◽  
Deepak Upreti ◽  
Sam K. P. Kung
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
Cell Recruitment ◽  
Cross Presentation ◽  
Cell Immunity ◽  
Immune Cell Recruitment

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

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