Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 27, 2025

Background There is no neoadjuvant immunotherapy for early-stage oral cancer patients. We report a single-arm, open-label, pilot clinical trial assessing the efficacy and safety of topical toll-like receptor-7 (TLR-7) agonist, imiquimod, utilized in setting squamous cell carcinoma (OSCC). Methods The primary endpoint reduction tumor counts assessed by quantitative multiplex immunofluorescence immune-related pathologic response. secondary safety. Results 60% patients experienced 50% or greater count post-treatment (95% CI = 32% to 84%). Similarly, had major response (irMPR) with two complete responses, 40% partial (PR) percent residual viable ranging from 25% 65%. An increase functional helper cytotoxic T-cells significantly contributed (R=0.54 0.55, respectively). treatment was well tolerated application site mucositis being most common adverse event (grades 1-3), grade 4 life-threatening event. median follow-up time 17 months 16 - not reached), one-year recurrence-free survival 93% evaluable Conclusion Neoadjuvant imiquimod could be safe promising regimen cancer. Trial registration ClinicalTrials.gov, Identifier NCT04883645.

Язык: Английский

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From silent partners to potential therapeutic targets: macrophages in colorectal cancer

Cancer Immunology Immunotherapy, Год журнала: 2025, Номер 74(4)

Опубликована: Фев. 25, 2025

Cancer cells grow and survive in the tumor microenvironment, which is a complicated process. As key part of how colorectal cancer (CRC) progresses, tumor-associated macrophages (TAMs) exhibit double role. Through angiogenesis, this TAM can promote growth cancers. Although being able to modify adjust immune great advantage, these also anti-cancer properties including direct killing cells, presenting antigens, aiding T cell-mediated responses. The delicate regulatory mechanisms between system tumors are composed complex network pathways regulated by several factors hypoxia, metabolic reprogramming, cytokine/chemokine signaling, cell interactions. Decoding figuring out systems become significant building targeted treatment programs. Targeting TAMs CRC involves disrupting chemokine signaling or adhesion molecules, reprogramming them an anti-tumor phenotype using TLR agonists, CD40 modulation, selectively removing subsets that growth. Multi-drug resistance, absence accurate biomarker, drug non-specificity major problems. Combining macrophage-targeted therapies with chemotherapy immunotherapy may revolutionize treatment. Macrophage studies will advance new technology multi-omics methodologies help us understand build specific efficient treatments.

Язык: Английский

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Beyond the beat: A pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health

Current Problems in Cardiology, Год журнала: 2023, Номер 49(2), С. 102222 - 102222

Опубликована: Ноя. 23, 2023

Язык: Английский

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Comprehensive overview of utilizing metal-organic frameworks (MOFs) for precise cancer drug delivery

Microchemical Journal, Год журнала: 2024, Номер 204, С. 111056 - 111056

Опубликована: Июнь 24, 2024

Язык: Английский

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Nanocarrier-based targeting of metabolic pathways for endometrial cancer: Status and future perspectives

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115348 - 115348

Опубликована: Авг. 26, 2023

Cancer is the second-most lethal global disease, as per health reports, and responsible for around 70% of deaths in low- middle-income countries. Endometrial cancer one emerging malignancies has been predicted a public challenge future. Insulin resistance, obesity, diabetes mellitus are key metabolic factors that promote risks development endometrial cancer. Various signaling pathways associated genes involved genesis cancer, any mutation or deletion such related leads to induction The conventional way drug delivery used ages but with poor management due non-targeting cells, low efficacy therapy, toxicity issues well. In this context, nanocarrier-based therapy an effective alternate choice overcomes problems therapy. review article, we highlighted targeting special focus on various pathways. Furthermore, future perspectives were also underpinned. It concluded via nanocarrier scaffolds pharmaceutical design significant treatment

Язык: Английский

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Tumor-associated macrophages as a potential therapeutic target in thyroid cancers

Cancer Immunology Immunotherapy, Год журнала: 2023, Номер 72(12), С. 3895 - 3917

Опубликована: Окт. 5, 2023

Язык: Английский

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Mechanism-Driven Design of Multispecific Antibodies for Targeted Disease Treatment

Annual Review of Chemical and Biomolecular Engineering, Год журнала: 2024, Номер 15(1), С. 105 - 138

Опубликована: Янв. 26, 2024

Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand utility antibody therapies, significant efforts have been invested in designing multispecific multiple targets using single molecule. These culminated remarkable translational progress, including nine US Food and Drug Administration–approved with countless others various stages preclinical or clinical development. In this review, we discuss several categories antibodies that achieved approval shown promise earlier We focus on molecular mechanisms used by how these inform their customized design formulation. particular, target disease markers, multiparatopic immune-interfacing antibodies. Overall, innovative designs are fueling exciting advances across immunotherapeutic landscape.

Язык: Английский

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Macrophages as a Source and Target of GDF-15

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7313 - 7313

Опубликована: Июль 3, 2024

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 involved in immune tolerance and elevated several acute chronic stress conditions, often correlating with disease severity patient prognosis cancer172 metabolic cardiovascular disorders. Despite these clinical associations, molecular mechanisms orchestrating its effects remain be elucidated. The of are pleiotropic but cell-specific dependent on microenvironment. While expression can stimulated by inflammatory mediators, predominant were reported as anti-inflammatory pro-fibrotic. role macrophage system has been increasingly investigated recent years. Macrophages produce high levels during oxidative lysosomal stress, which lead fibrogenesis angiogenesis at tissue level. At same time, macrophages respond switching their phenotype tolerogenic one. Several GDF-15-based therapies under development, including analogs/mimetics GDF-15-targeting monoclonal antibodies. In this review, we summarize major physiological pathological contexts interacts macrophages. We also discuss challenges future perspectives therapeutic translation GDF-15.

Язык: Английский

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Targeting Tumor-Associated Macrophages with the Immune-Activating Nanomedicine for Achieving Strong Antitumor Activity with Rapid Clearance from the Body

ACS Nano, Год журнала: 2024, Номер 18(34), С. 23757 - 23772

Опубликована: Авг. 14, 2024

Toll-like receptors (TLRs) are a class of pattern recognition (PRRs) crucial for the detection infections and activation downstream signaling pathways that lead to production pro-inflammatory cytokines interferons. The TLR pathway is an attractive actively studied target pathway. Because their strong immunostimulatory activity, TLRs thought be "double-edged sword" systemic treatment, even in cancer field. To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) deliver TLR7 agonist DSP-0509. We used low molecular weight dextran CD206 high M2-type macrophages, activate them, induce change phenotype antitumor M1-type with rapid clearance from body astonishing activity. also demonstrated effect our best drug candidate 5DEX-0509R dependent on abundance TAMs, consistent mechanism action. believe generated by D-TAC technology can clinically applicable immunotherapy

Язык: Английский

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New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities

International Journal of Cancer, Год журнала: 2024, Номер unknown

Опубликована: Сен. 22, 2024

Abstract Approximately one‐third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective seminal studies on metastasis RCC describing the main molecular modulators and growth factor signaling pathways most important for RCC‐stimulated osteoclast‐mediated destruction. We next focus newer developments revealing with in‐depth details, bidirectional interplay between cancer cells immune stromal microenvironment that can through epigenetic reprogramming, profoundly affect behaviors transformed cells. Understanding their mechanistic interactions is paramount importance advancing both fundamental translational research. These new investigations into landscape RCC‐bone offer novel insights identify potential avenues future therapeutic interventions.

Язык: Английский

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