Research progress of interleukin-15 in cancer immunotherapy

Cai, Menghan; Huang, Xuan; Huang, Xin; Ju, Dianwen; Zhu, Yi‐Zhun; Li, Ye

doi:10.3389/fphar.2023.1184703

Cited by 24 publications

(11 citation statements)

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“…S5 ). Considering lymphocytes contribute to most of the IL-15 related anti-tumor activity ( 45 ) and IL-6 was one of the key factor to cytokine related toxicity ( 46, 47 ), these phenomena may explain why mRNA-LNP showed lower toxicity in vivo . Furthermore, the levels of red blood cells, hemoglobin, and platelets in the mRNA-LNP groups were all detected within the normal range ( fig.…”

Section: Resultsmentioning

confidence: 99%

Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy

Yu,

Li,

Luo

et al. 2024

Preprint

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Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate in oncology because of its pivotal role in modulating both innate and adaptive immunity. However, the therapeutic utility remains concern due to the unexpected toxicity. We propose here that the mRNA lipid nanoparticle (mRNA-LNP) system can balance the issue through targeted delivery to increase IL-15 concentration in the tumor area and reduce leakage into the circulation. Utilizing the Structure-driven TARgeting (STAR) platform, we acquired intellectual property LNP vectors for effective and selective mRNA delivery to local (LNPLocal) and to pulmonary (LNPLung). Then the promising IL-15 superagonists mRNAs were obtained through structural optimization and sequence screening, showing better activity compared with benchmarker N-803. Subsequently, the anti-tumor efficacy of IL-15 superagonists mRNAs were evaluated by intratumoural (i.t.) injection and intravenous (i.v.) injection via LNPLocal and LNPLung, respectively. As a result, such superagonists exhibited better anti-tumor activity, less systematic exposure, and less cytokine related risks than N-803. We finally verified the selective delivery and well tolerability of LNPLung in non-human primates (NHPs), confirming the potential for clinical application. This finding may open up new possibilities for the treatment of lung cancers and lung metastasis cancers.

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Section: Resultsmentioning

confidence: 99%

Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy

Yu,

Li,

Luo

et al. 2024

Preprint

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“…The secretion of IL-15 from muscle is not necessarily dependent on transcriptional changes in its mRNA, and the intramuscular pool of secretable IL-15 could be the primary source of IL-15 following exercise ( 32 , 35 , 71 ). It is considered that IL-15 is a promising target in the treatment of metabolic disorders through improvements in lipid and glucose metabolism, and pharmacologically beneficial in cancer immunotherapy through anti-tumor activity ( 20 , 72 , 73 ). Since IL-15 is a myokine with significant metabolic, anabolic, and immune functions ( 20 , 74 ), exercise-induced changes might be beneficial for prevention and management of metabolic disorders in humans.…”

Section: Discussionmentioning

confidence: 99%

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

Khalafi,

Maleki,

Symonds

et al. 2024

Front. Immunol.

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

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“…The emergence of IL-15 immunotherapies for the treatment of cancer provides a range of therapeutic options for potential repurposing in NS [128,129]. In addition to recombinant human IL-15, nearly ten IL-15 agonists have been successfully developed and clinically studied [130]. IL-15 immunotherapies display a range of potencies, half-lives and modes of action, which may be of value across the spectrum of NS [129].…”

Section: Cytoprotective Effects Of Interleukins In Ns: Il-rγc Superfa...mentioning

confidence: 99%

Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome

Kovalik,

Dacanay,

Crowley

et al. 2024

Biomedicines

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Interleukins are a family of 40 bioactive peptides that act through cell surface receptors to induce a variety of intracellular responses. While interleukins are most commonly associated with destructive, pro-inflammatory signaling in cells, some also play a role in promoting cellular resilience and survival. This review will highlight recent evidence of the cytoprotective actions of the interleukin 1 receptor (IL-1R)- and common gamma chain receptor (IL-Rγc)-signaling cytokines in nephrotic syndrome (NS). NS results from the injury or loss of glomerular visceral epithelial cells (i.e., podocytes). Although the causes of podocyte dysfunction vary, it is clear that pro-inflammatory cytokines play a significant role in regulating the propagation, duration and severity of disease. Pro-inflammatory cytokines signaling through IL-1R and IL-Rγc have been shown to exert anti-apoptotic effects in podocytes through the phosphoinositol-3-kinase (PI-3K)/AKT pathway, highlighting the potential utility of IL-1R- and IL-Rγc-signaling interleukins for the treatment of podocytopathy in NS. The paradoxical role of interleukins as drivers and mitigators of podocyte injury is complex and ill-defined. Emerging evidence of the cytoprotective role of some interleukins in NS highlights the urgent need for a nuanced understanding of their pro-survival benefits and reveals their potential as podocyte-sparing therapeutics for NS.

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Research progress of interleukin-15 in cancer immunotherapy

Cited by 24 publications

References 100 publications

Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy

Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy

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

Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome

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