Bioorthogonal-Activated In Situ Vaccine Mediated by a COF-Based Catalytic Platform for Potent Cancer Immunotherapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5330 - 5341

Published: Feb. 23, 2023

Personalized tumor vaccines have become a promising modality for cancer immunotherapy. However, in situ personalized generated from immunogenic cell death (ICD) and adjuvants are mired by toxic side effects unsatisfactory efficiency. Herein, functionalizing the reticular structure to optimize catalytic activity of materials, series biocompatible covalent organic framework (COF)-based catalysts been designed screened establishing bioorthogonal-activated vaccine an efficient safe way. Especially, pro-doxorubicin (pro-DOX) could be bioorthogonally activated COF-based Fe(II) catalysts, which elicited ICD released tumor-associated antigens (TAAs). This prodrug activation strategy minimize drug maximize treatment effects. More importantly, system also catalytically activate pro-imiquimod (pro-IMQ, TLR7/8 immune agonist), served as adjuvant amplify antitumor immunity. Notably, this not only facilitated strong response but prevented dose-dependent chemotherapeutic drugs, including systemic inflammation caused random distribution adjuvants. To best our knowledge, it is first time devise platform generating vaccine, would provide paradigm achieving secure robust

Language: Английский

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tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(10), P. 1433 - 1444

Published: Sept. 22, 2022

Language: Английский

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Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Language: Английский

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Polysaccharides regulate Th1/Th2 balance: A new strategy for tumor immunotherapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 115976 - 115976

Published: Dec. 3, 2023

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 are two key subsets of Th that exist relative equilibrium through the secretion cytokines suppress respective response. When type cytokine tumor microenvironment is altered, this may be disrupted, leading a shift from Th1/Th2 imbalance one decisive factors development malignant tumors. Therefore, focusing on balance responses enable future breakthroughs cancer immunotherapy. Polysaccharides can regulate between characteristic profiles, thereby improving microenvironment. To our knowledge, study most comprehensive assessment regulation by polysaccharides. Herein, we systematically summarized intrinsic molecular mechanisms polysaccharides provide new perspective potential target drugs for improved immunity delayed progression.

Language: Английский

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Engineering the IL‐4/IL‐13 axis for targeted immune modulation

Immunological Reviews, Journal Year: 2023, Volume and Issue: 320(1), P. 29 - 57

Published: June 7, 2023

The structurally and functionally related interleukin-4 (IL-4) IL-13 cytokines play pivotal roles in shaping immune activity. IL-4/IL-13 axis is best known for its critical role T helper 2 (Th2) cell-mediated Type inflammation, which protects the host from large multicellular pathogens, such as parasitic helminth worms, regulates responses to allergens. In addition, IL-4 stimulate a wide range of innate adaptive cells, well non-hematopoietic coordinate various functions, including regulation, antibody production, fibrosis. Due importance broad spectrum physiological activities, network has been targeted through variety molecular engineering synthetic biology approaches modulate behavior develop novel therapeutics. Here, we review ongoing efforts manipulate axis, cytokine strategies, formulation fusion proteins, antagonist development, cell approaches, biosensor design. We discuss how these strategies have employed dissect pathways, discover new immunotherapies targeting allergy, autoimmune diseases, cancer. Looking ahead, emerging bioengineering tools promise continue advancing fundamental understanding enabling researchers exploit insights effective interventions.

Language: Английский

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Targeting immunometabolism against acute lung injury

Clinical Immunology, Journal Year: 2023, Volume and Issue: 249, P. 109289 - 109289

Published: March 12, 2023

Language: Английский

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Cellular metabolism regulates the differentiation and function of T-cell subsets

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(5), P. 419 - 435

Published: April 2, 2024

Abstract T cells are an important component of adaptive immunity and protect the host from infectious diseases cancers. However, uncontrolled cell may cause autoimmune disorders. In both situations, antigen-specific undergo clonal expansion upon engagement activation antigens. Cellular metabolism is reprogrammed to meet increase in bioenergetic biosynthetic demands associated with effector expansion. Metabolites not only serve as building blocks or energy sources fuel growth but also regulate a broad spectrum cellular signals that instruct differentiation multiple subsets. The realm immunometabolism research undergoing swift advancements. Encapsulating all recent progress within this concise review possible. Instead, our objective provide succinct introduction swiftly progressing research, concentrating on metabolic intricacies three pivotal nutrient classes—lipids, glucose, amino acids—in cells. We shed light investigations elucidating roles these groups metabolites mediating immune functions Moreover, we delve into prospect “editing” pathways using pharmacological genetic approaches, aim synergizing approach existing immunotherapies enhancing efficacy antitumor antiinfection responses.

Language: Английский

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Critical role of the gut microbiota in immune responses and cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 14, 2024

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence connections between and cancer immunotherapy. Therefore, understanding functional regulating immune responses to immunotherapy is crucial for developing precision medicine. this review, we extract insights from state-of-the-art research decipher complicated crosstalk among microbiota, systemic system, context Additionally, as can account immune-related adverse events, discuss potential interventions minimize these effects clinical application five microbiota-targeted strategies that precisely increase efficacy Finally, holds promising target immunotherapeutics, summarize current challenges provide general outlook on future directions field.

Language: Английский

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Current and future immunotherapeutic approaches in pancreatic cancer treatment

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Language: Английский

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Nutrients: Signal 4 in T cell immunity

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(3)

Published: Feb. 27, 2024

T cells are integral in mediating adaptive immunity to infection, autoimmunity, and cancer. Upon immune challenge, exit from a quiescent state, followed by clonal expansion effector differentiation. These processes shaped three established signals, namely antigen stimulation (Signal 1), costimulation 2), cytokines 3). Emerging findings reveal that nutrients, including glucose, amino acids, lipids, crucial regulators of cell responses interplay with Signals 1-3, highlighting nutrients as Signal 4 license immunity. Here, we first summarize the functional importance underlying mechanisms nutrient transport, sensing, signaling orchestrating activation quiescence exit. We also discuss roles programming differentiation fitness how can be targeted improve disease therapy. Understanding respond microenvironments will provide insights into context-dependent functions therapeutic interventions.

Language: Английский

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