Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10

Anticancer Research, Год журнала: 2021, Номер 41(7), С. 3247 - 3252

Опубликована: Июль 1, 2021

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as anticancer therapy for longer than most other cancer modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents superseded by other, more efficacious such immune checkpoint inhibitors. Several issues persist with cytokine-based therapies; these broadly categorised into a) high toxicity b) low efficacy. moderate benefits early therapies, advances in molecular engineering, genomics, analysis hold promise optimise reinstate therapies future clinical practice. This review considers five important concepts successful application including: (i) improving pharmacokinetics pharmacodynamics, (ii) local administration strategies, (iii) understanding context-dependent interactions tumour-microenvironment, (iv) elucidating role genetic polymorphisms, (v) optimising combination therapies. IL-10 has focus attention recent years discussed herein example.

Язык: Английский

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Native and Bioengineered Exosomes for Ischemic Stroke Therapy

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Март 23, 2021

Exosomes are natural cells-derived vesicles, which at the forefront toward clinical success for various diseases, including cerebral ischemia. mediate cell-to-cell communication in different brain cells during both physiological and pathological conditions. an extensively studied type of extracellular vesicle, considered to be best alternative stem cell–based therapy. They can secreted by cell types have unique biological properties. Even though native exosomes potential ischemic stroke therapy, some undesirable features prevent their applications, a short half-life, poor targeting property, low concentration target site, rapid clearance from lesion region, inefficient payload. In this review, we highlight exosome trafficking cellular uptake survey latest discoveries context research as fit owing its brain-homing abilities. Furthermore, overview methods researchers bioengineered (BioEng-Exo) Finally, summarize studies were third party recovery. This review provides up-to-date knowledge about versatile nature with special focus on BioEng-Exo stroke. Standard bioengineering techniques mandatory future will lead

Язык: Английский

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β‐catenin‐controlled tubular cell‐derived exosomes play a key role in fibroblast activation via the OPN‐CD44 axis

Journal of Extracellular Vesicles, Год журнала: 2022, Номер 11(3)

Опубликована: Март 1, 2022

Abstract Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD), suggesting intimate communication between two types cells. However, underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins other materials recipient In our study, we found that exosomes were aroused by β‐catenin renal tubular Osteopontin (OPN), especially its N‐terminal fragment (N‐OPN), was encapsulated β‐catenin‐controlled cell‐derived exosome cargo, subsequently passed fibroblasts. Through binding with CD44, exosomal OPN promoted proliferation activation. Gene deletion cells (Ksp‐β‐catenin −/− ) or gene ablation CD44 (CD44 greatly ameliorated fibrosis. Notably, N‐OPN carried secreted into urine patients CKD, negatively correlated function. The urinary from CKD accelerated fibrosis, which blocked deletion. These results suggest exosome‐mediated OPN/CD44 axis plays key is controlled β‐catenin.

Язык: Английский

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CD73 in small extracellular vesicles derived from HNSCC defines tumour‐associated immunosuppression mediated by macrophages in the microenvironment

Journal of Extracellular Vesicles, Год журнала: 2022, Номер 11(5)

Опубликована: Май 1, 2022

Abstract Research on tumour cell‐derived small extracellular vesicles (sEVs) that regulate microenvironment (TME) has provided strategies for targeted therapy of head and neck squamous cell carcinoma (HNSCC). Herein, we demonstrated sEVs derived from HNSCC cancer cells carried CD73 (sEVs ), which promoted malignant progression mediated immune evasion. The phagocytosed by tumour‐associated macrophages (TAMs) in the TME induced immunosuppression. Higher high TAMs infiltration levels were correlated with poorer prognosis, while activated NF‐κB pathway TAMs, thereby inhibiting function increasing cytokines secretion such as IL‐6, IL‐10, TNF‐α, TGF‐β1. absence enhanced sensitivity anti‐PD‐1 through reversed Moreover, circulating increased risk lymph node metastasis worse prognosis. Taken together, our study suggests contributes to immunosuppression is a potential predictor responses checkpoint HNSCC.

Язык: Английский

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Advances in Extracellular Vesicle Nanotechnology for Precision Theranostics

Advanced Science, Год журнала: 2022, Номер 10(3)

Опубликована: Ноя. 14, 2022

Abstract Extracellular vesicles (EVs) have increasingly been recognized as important cell surrogates influencing many pathophysiological processes, including cellular homeostasis, cancer progression, neurologic disease, and infectious disease. These behaviors enable EVs broad application prospects for clinical in disease diagnosis treatment. Many studies suggest that are superior to conventional synthetic carriers terms of drug delivery circulating biomarkers early diagnosis, opening up new frontiers modern theranostics. Despite these potential, containing diverse components, such nucleic acids, proteins, metabolites highly heterogeneous small size. The limitation preparatory, engineering analytical technologies poses technical barriers translation. This article aims at present a critical overview emerging field biomedical applications challenges involved their clinic translations. current methods isolation identification discussed. Additionally, strategies developed enhance scalable production improved cargo loading well tumor targeting presented. potential EVs, particularly different origins the next generation diagnostic treatment platforms, clarified.

Язык: Английский

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