Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Engineering Strategies for Immunomodulatory Cytokine Therapies – Challenges and Clinical Progress

ABSTRACT: Cytokines are immunoregulatory proteins involved in many pathological states with promising potential as therapeutic agents. A diverse array of cytokines have been studied in preclinical disease models since the 1950s, some of which became successful biopharmaceutical products with the advancement of recombinant protein technology in the 1980s. However, following these early approvals, clinical translation of these natural immune signaling molecules has been limited due to their pleiotropic action in many cell types, and the fact that they have evolved to act primarily locally in tissues. These characteristics, combined with poor pharmacokinetics, have hindered the delivery of cytokines via systemic administration routes due to dose-limiting toxicities. However, given their clinical potential and recent clinical successes in cancer immunotherapy, cytokines continue to be extensively pursued in preclinical and clinical studies, and a range of molecular and formulation engineering strategies are being applied to reduce treatment toxicity while maintaining or enhancing therapeutic efficacy. This review provides a brief background on the characteristics of cytokines and their history as clinical therapeutics, followed by a deeper discussion on the engineering strategies developed for cytokine therapies with a focus on the translational relevance of these approaches. Graphical Abstract

SUBMITTER: Pires I

PROVIDER: S-EPMC8562465 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress.

Project description:Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like cells that can differentiate into cells of multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs can be found in nearly all tissues but mostly located in perivascular niches, playing a significant role in tissue repair and regeneration. Additionally, MSCs interact with immune cells both in innate and adaptive immune systems, modulating immune responses and enabling immunosuppression and tolerance induction. Understanding the biology of MSCs and their roles in clinical treatment is crucial for developing MSC-based cellular therapy for a variety of pathological conditions. Here, we review the progress in the study on the mechanisms underlying the immunomodulatory and regenerative effects of MSCs; update the medical translation of MSCs, focusing on the registration trials leading to regulatory approvals; and discuss how to improve therapeutic efficacy and safety of MSC applications for future.

| S-EPMC7414268 | biostudies-literature

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives.

Project description:Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

| S-EPMC10507240 | biostudies-literature

Molecular targeting therapies for neuroblastoma: Progress and challenges.

Project description:There is an urgent need to identify novel therapies for childhood cancers. Neuroblastoma is the most common pediatric solid tumor, and accounts for ~15% of childhood cancer-related mortality. Neuroblastomas exhibit genetic, morphological and clinical heterogeneity, which limits the efficacy of existing treatment modalities. Gaining detailed knowledge of the molecular signatures and genetic variations involved in the pathogenesis of neuroblastoma is necessary to develop safer and more effective treatments for this devastating disease. Recent studies with advanced high-throughput "omics" techniques have revealed numerous genetic/genomic alterations and dysfunctional pathways that drive the onset, growth, progression, and resistance of neuroblastoma to therapy. A variety of molecular signatures are being evaluated to better understand the disease, with many of them being used as targets to develop new treatments for neuroblastoma patients. In this review, we have summarized the contemporary understanding of the molecular pathways and genetic aberrations, such as those in MYCN, BIRC5, PHOX2B, and LIN28B, involved in the pathogenesis of neuroblastoma, and provide a comprehensive overview of the molecular targeted therapies under preclinical and clinical investigations, particularly those targeting ALK signaling, MDM2, PI3K/Akt/mTOR and RAS-MAPK pathways, as well as epigenetic regulators. We also give insights on the use of combination therapies involving novel agents that target various pathways. Further, we discuss the future directions that would help identify novel targets and therapeutics and improve the currently available therapies, enhancing the treatment outcomes and survival of patients with neuroblastoma.

| S-EPMC7906923 | biostudies-literature

Fiber-based tissue engineering: Progress, challenges, and opportunities.

Project description:Tissue engineering aims to improve the function of diseased or damaged organs by creating biological substitutes. To fabricate a functional tissue, the engineered construct should mimic the physiological environment including its structural, topographical, and mechanical properties. Moreover, the construct should facilitate nutrients and oxygen diffusion as well as removal of metabolic waste during tissue regeneration. In the last decade, fiber-based techniques such as weaving, knitting, braiding, as well as electrospinning, and direct writing have emerged as promising platforms for making 3D tissue constructs that can address the abovementioned challenges. Here, we critically review the techniques used to form cell-free and cell-laden fibers and to assemble them into scaffolds. We compare their mechanical properties, morphological features and biological activity. We discuss current challenges and future opportunities of fiber-based tissue engineering (FBTE) for use in research and clinical practice.

| S-EPMC3631569 | biostudies-literature

Kinase-targeted cancer therapies: progress, challenges and future directions.

Project description:The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies.

| S-EPMC5817855 | biostudies-literature

Engineering of obligate intracellular bacteria: progress, challenges and paradigms.

Project description:It is estimated that approximately one billion people are at risk of infection with obligate intracellular bacteria, but little is known about the underlying mechanisms that govern their life cycles. The difficulty in studying Chlamydia spp., Coxiella spp., Rickettsia spp., Anaplasma spp., Ehrlichia spp. and Orientia spp. is, in part, due to their genetic intractability. Recently, genetic tools have been developed; however, optimizing the genomic manipulation of obligate intracellular bacteria remains challenging. In this Review, we describe the progress in, as well as the constraints that hinder, the systematic development of a genetic toolbox for obligate intracellular bacteria. We highlight how the use of genetically manipulated pathogens has facilitated a better understanding of microbial pathogenesis and immunity, and how the engineering of obligate intracellular bacteria could enable the discovery of novel signalling circuits in host-pathogen interactions.

| S-EPMC5557331 | biostudies-literature

Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.

Project description:Restoration of insulin independence and normoglycemia has been the overarching goal in diabetes research and therapy. While whole-organ and islet transplantation have become gold-standard procedures in achieving glucose control in diabetic patients, the profound lack of suitable donor tissues severely hampers the broad application of these therapies. Here, we describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies.

| S-EPMC6007036 | biostudies-literature

Application of MultiStem(®) Allogeneic Cells for Immunomodulatory Therapy: Clinical Progress and Pre-Clinical Challenges in Prophylaxis for Graft Versus Host Disease.

Project description:The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC) for treatment of Graft versus Host Disease (GvHD), and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal(®); Osiris Therapeutics). This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT) to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem(®) product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products/donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

| S-EPMC3506828 | biostudies-literature

Magnetic nanoparticles for oligodendrocyte precursor cell transplantation therapies: progress and challenges.

Project description:Oligodendrocyte precursor cells (OPCs) have shown high promise as a transplant population to promote regeneration in the central nervous system, specifically, for the production of myelin - the protective sheath around nerve fibers. While clinical trials for these cells have commenced in some areas, there are currently key barriers to the translation of neural cell therapies. These include the ability to (a) image transplant populations in vivo; (b) genetically engineer transplant cells to augment their repair potential; and (c) safely target cells to sites of pathology. Here, we review the evidence that magnetic nanoparticles (MNPs) are a 'multifunctional nanoplatform' that can aid in safely addressing these translational challenges in neural cell/OPC therapy: by facilitating real-time and post-mortem assessment of transplant cell biodistribution, and biomolecule delivery to transplant cells, as well as non-invasive 'magnetic cell targeting' to injury sites by application of high gradient fields. We identify key issues relating to the standardization and reporting of physicochemical and biological data in the field; we consider that it will be essential to systematically address these issues in order to fully evaluate the utility of the MNP platform for neural cell transplantation, and to develop efficacious neurocompatible particles for translational applications.

| S-EPMC4452053 | biostudies-literature

Clinical progress of nanomedicine-based RNA therapies.

Project description:The clinical application of nanoparticles (NPs) to deliver RNA for therapy has progressed rapidly since the FDA approval of Onpattro® in 2018 for the treatment of polyneuropathy associated with hereditary transthyretin amyloidosis. The emergency use authorization or approval and widespread global use of two mRNA-NP based vaccines developed by Moderna Therapeutics Inc. and Pfizer-BioNTech in 2021 has highlighted the translatability of NP technology for RNA delivery. Furthermore, in clinical trials, a wide variety of NP formulations have been found to extend the half-life of RNA molecules such as microRNA, small interfering RNA, and messenger RNA, with limited safety issues. In this review, we discuss the NP formulations that are already used in the clinic to deliver therapeutic RNA and highlight examples of RNA-NPs which are currently under evaluation for human use. We also detail NP formulations that failed to progress through clinical trials, in hopes of guiding future successful translation of nanomedicine-based RNA therapeutics into the clinic.

| S-EPMC8897211 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data