IL-2-driven CD8+ T cell phenotypes: implications for immunotherapy

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(11), P. 890 - 901

Published: Oct. 10, 2023

The therapeutic potential of interleukin (IL)-2 in cancer treatment has been known for decades, yet its widespread adoption clinical practice remains limited. Recently, chimeric proteins an anti-PD-1 antibody and suboptimal IL-2 variants were shown to stimulate potent antitumor antiviral immunity by inducing unique effector CD8

Language: Английский

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Interleukin-15 responses to acute and chronic exercise in adults: a systematic review and meta-analysis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 3, 2024

Purpose Interlukin-15 (IL-15) is an inflammatory cytokine that plays a vital role in immunology and obesity-associated metabolic syndrome. We performed this systematic review meta-analysis to investigate whether exercise promotes circulating IL-15 concentrations adults. Methods searched PubMed, Web of Science, Scopus from inception May, 2023 identified original studies investigated the effectiveness acute and/or chronic on serum/plasma levels Standardized mean differences (SMD) 95% confidence intervals (CI) were calculated using random effect models. Subgroup analyses based type exercise, training status, health status body mass indexes (BMI) participants. Results Fifteen involving 411 participants 12 899 included analyses, respectively. Our findings showed increased immediately after compared with baseline [SMD=0.90 (95% CI: 0.47 1.32), p=0.001], regardless participants’ status. Similarly, was also associated even one-hour [SMD=0.50 0.00 0.99), p=0.04]. Nevertheless, did not have significant [SMD=0.40 -0.08 0.88), p=0.10]. Conclusion results confirm effective increasing intervention, thereby playing potential improving metabolism Systematic registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=445634 , identifier CRD42023445634.

Language: Английский

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Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316790 - e0316790

Published: Jan. 14, 2025

Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune production proliferation. It has been combined mAbs other immunotherapies improve efficacy reduce side effects. Fusion of anti-PD-1 mAb IL-15 streamlines drug administration management. In this study, we developed a prototype by conjugating the receptor subunit alpha (IL-15Rα) complex C-terminus Pembrolizumab (Pembrolizumab-IL-15Rα-IL15) using plant molecular farming for production. LC-MS revealed presence N -glycans (GnGnXF, GnXF Man9GlcNAc2) on molecule, which may affect receptor-binding avidity. However, ELISA demonstrated comparable binding Pembrolizumab-IL-15Rα-IL15 human PD-1 protein as commercial Pembrolizumab. mouse anti-cancer (3 mg kg -1 ) exhibited slightly improved tumor-growth inhibition, reducing tumor size 94% compared (5 83% reduction, regardless statistically significant difference. conclusion, Pembrolizumab-IL-15Rα-IL-15 was successfully produced shows promise addressing enhancing immunomodulatory effects payload.

Language: Английский

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IL-15 as a key regulator in NK cell-mediated immunotherapy for cancer: From bench to bedside

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112156 - 112156

Published: April 25, 2024

Language: Английский

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Cytokine Profile in Lung Cancer Patients: Anti-Tumor and Oncogenic Cytokines

Cancers, Journal Year: 2023, Volume and Issue: 15(22), P. 5383 - 5383

Published: Nov. 13, 2023

Lung cancer is currently the second leading cause of death worldwide. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding tumor microenvironment (TMJ) or immune system surrounding needed. Cytokines are small proteins that carry messages between cells and known to play an important role in body’s response inflammation infection. for immunity lung cancer. They promote growth (oncogenic cytokines) inhibit (anti-tumour by controlling signaling pathways growth, proliferation, metastasis, apoptosis. The relies heavily on cytokines. can also be produced laboratory therapeutic use. Cytokine therapy helps stop kill cells. Interleukins interferons two types cytokines used treat This article begins addressing TMJ its components review highlights functions various such interleukins (IL), transforming factor (TGF), necrosis (TNF).

Language: Английский

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The Regular Consumption of a Food Supplement Containing Miraculin Can Contribute to Reducing Biomarkers of Inflammation and Cachexia in Malnourished Patients with Cancer and Taste Disorders: The CLINMIR Pilot Study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract Background Taste disorders are common in patients with cancer undergoing systemic therapy, persist during treatment and associated reduced food intake, increasing the risk of malnutrition. Cachectic syndrome, which is these characterized by marked weight loss, anorexia, asthenia anemia, linked to presence growth tumor leads inflammation. Synsepalum dulcificum a plant whose berries contain miraculin, glycoprotein that transforms sour tastes into sweet ones could serve ameliorate taste cancer. Objective To evaluate effect regular intake Dried Miracle Berries (DMB), novel containing on several biomarkers inflammation cachexia malnourished receiving antineoplastic therapy. Materials methods Triple-blind, randomized, placebo-controlled clinical trial. Thirty-one various etiologies chemotherapy were enrolled pilot study divided three groups. The first group received tablet 150 mg DMB (standard dose); high-dose 300 DMB, third placebo for months before each main meal. Plasma levels molecules measured using X-MAP Luminex multiplexing platform. Results groups showed decrease plasma IL-6, IL-1β, TNF-α, PIF throughout intervention, although percentage change from baseline was greater standard dose DMB. In contrast, CNTF concentration only decreased standard-dose group. This also presented greatest reduction IL-6/ IL-10 ratio, while IL-15 increased treated but not placebo. Regardless consumption, sTNFR-II tended who responsed well treatment. We did find significant correlations between cytokines sensory variables or dietary nutritional status. Conclusions consumption supplement miraculin along can contribute reducing exhibiting disorders.

Language: Английский

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Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9448 - 9448

Published: Aug. 30, 2024

FMS-like tyrosine kinase 3 (FLT3) mutations are genetic changes found in approximately thirty percent of patients with acute myeloid leukemia (AML). FLT3 AML represent a challenging clinical scenario characterized by high rate relapse, even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The advent inhibitors (TKIs), such as midostaurin and gilteritinib, has shown promise achieving complete remission. However, substantial proportion still experience relapse following TKI treatment, necessitating innovative therapeutic strategies. This review critically addresses the current landscape treatments for FLT3+ AML, particular focus on gilteritinib. Gilteritinib, highly selective inhibitor, demonstrated efficacy targeting mutant receptor, thereby inhibiting aberrant signaling pathways that drive leukemic proliferation. monotherapy TKIs may not be sufficient to eradicate blasts. Specifically, we provide evidence integrating gilteritinib mammalian targets rapamycin (mTOR) interleukin-15 (IL-15) complexes. combination mTOR inhibitors, IL-15 complexes presents compelling strategy enhance eradication blasts NK killing, offering potential improved patient outcomes.

Language: Английский

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Effects of short- and long-term exercise training on cancer cells in vitro: Insights into the mechanistic associations

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2024, Volume and Issue: 14, P. 100994 - 100994

Published: Oct. 5, 2024

Exercise is a therapeutic approach in cancer treatment, providing several benefits. Moreover, exercise associated with reduced risk for developing range of cancers and their recurrence, as well improving survival, even though the underlying mechanisms remain unclear. Preclinical clinical evidence shows that acute effects single session can suppress growth various cell lines vitro. This suppression potentially due to altered concentrations hormones (e.g., insulin) cytokines tumor necrosis factor alpha interleukin 6) after exercise. These factors, known be involved tumorigenesis, may explain why incidence, mortality. However, short- (<8 weeks) long-term (≥8 programs on cells have been reported mixed results. Although more research needed, it appears interventions incorporating both diet seem greater inhibitory apparently healthy subjects patients. speculative, these suppressive driven by changes body weight composition reduction low-grade inflammation often sedentary behavior, low muscle mass, excess fat mass Taken together, such could alter systemic levels circulating leading less favorable environment tumorigenesis. While regular establish cancer-suppressive environment, each bout provides further "dose" anticancer medicine. Therefore, integrating play significant role management, highlighting need future investigations this promising area research.

Language: Английский

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A New Antibody–Cytokine Construct Targeting Natural Killer Cells: An Immunotherapeutic Approach to Chronic Lymphocytic Leukemia

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 117 - 117

Published: Jan. 13, 2025

In chronic lymphocytic leukemia (CLL), natural killer (NK) cells show a dysfunctional phenotype that correlates with disease progression. Our aim was to restore NK cell functionality in CLL through specifically targeted IL15-stimulating activity; IL15 targeting could, fact, potentiate the activity of and reduce off-target effects. We designed developed cis-acting immunocytokine composed an anti-CD56 single-chain Fragment variable (scFv) IL15, labeled scFvB1IL15. scFvB1IL15 tested vitro on peripheral blood mononuclear (PBMCs) obtained from both different healthy donors (HDs) patients order evaluate its ability target enhance their activation NK-mediated directed cytotoxicity. induced strong degranulation cytokine chemokine production HD- patient-derived PBMC samples. Furthermore, compared alone, it able induce higher levels NKG2D- NKp30-activating receptors direct killing The preliminary data presented this work suggest IL15’s via scFvB1 potentiates effects can be useful agent for overcoming functional gaps contribute NK-cell-based immunotherapies.

Language: Английский

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Efficacy of Anti-Cancer Immune Responses Elicited Using Tumor-Targeted IL-2 Cytokine and Its Derivatives in Combined Preclinical Therapies

Vaccines, Journal Year: 2025, Volume and Issue: 13(1), P. 69 - 69

Published: Jan. 13, 2025

Effective cancer therapies must address the tumor microenvironment (TME), a complex network of cells and stromal components, including endothelial, immune, mesenchymal cells. Durable outcomes require targeting both TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based have shown efficacy in cancers such as metastatic melanoma renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, antibody–drug conjugates, immunocytokines, antibody–cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8+ T lymphocytes natural killer (NK) cells, eliciting potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg activity further improve specificity reduce immunosuppression. Additionally, conjugates peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining immune checkpoint inhibitors (ICIs), agents, radiotherapy has demonstrated synergistic potential. Preclinical clinical studies highlight toxicity enhanced efficacy, overcoming TME-driven suppression. mitigate limitations high-dose soluble therapy, promoting activation adverse This review critically explores advances therapies, focusing on derivatives. Emphasis is placed their role combination strategies, showcasing potential to target effectively. Also, use immunocytokines “in situ” vaccination relieve immunosuppression discussed.

Language: Английский

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