Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling

Rossi, Jean‐François; Chiang, Hao-Chun; Levón, Kalle; Rhee, Frits van; Kanhai, Karan; Fajgenbaum, David C; Klein, Bernard

doi:10.3389/fimmu.2022.919489

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…This indicated that the prepared nanoparticles had a better siRNA transfection effect, improved the stability of siRNA in vivo , and exerted a better gene silencing effect. As a common cytokine in the tumor microenvironment, IL-6 plays a significant role in tumor angiogenesis, invasion and metastasis, immune escape, and other biological behaviors. − It has also been reported that it was involved in the regulation of tumor chemotherapy resistance . The increase in IL-6 gene expression will lead to drug resistance in vivo .…”

Section: Resultsmentioning

confidence: 99%

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

Wang,

Zhang,

et al. 2024

ACS Appl. Nano Mater.

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Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high immunogenicity. In this study, we developed a peptide-modified cyclodextrin-based nanosystem for co-delivery of celastrol and siPD-L1, named H4R6RGD-carboxymethyl-β-cyclodextrin@celastrol/siPD-L1 nanoparticles (H−C@C/siPD-L1 NPs). The cyclodextrin derivative could simultaneously utilize its cavity and positively charged chain to deliver siPD-L1 and celastrol (cela) through hydrophobic and electrostatic interactions. H−C@C/siPD-L1 NPs exhibited excellent stability and dispersibility. Characterization revealed that the nanoparticles exhibited a spherical morphology, displaying smooth surfaces and an average diameter of approximately 200 nm. The H−C@C/siPD-L1 NPs demonstrated enhanced cellular uptake and efficient lysosomal escape, thereby improving drug utilization while minimizing side effects on normal tissues. Furthermore, the H−C@C/siPD-L1 NPs facilitated the delivery of siPD-L1, effectively reducing the expression of PD-L1. This, in turn, promoted tumor apoptosis and augmented the antitumor effect through the endoplasmic reticulum (ER) stress-related apoptotic pathway. Notably, this multifunctional nanodrug delivery system, designed for the combination of chemotherapy and gene therapy, not only exhibited a potent antitumor effect but also improved the immunosuppressive microenvironment of the tumor. The targeted co-delivery of cela and siPD-L1 holds significant potential in advancing the application of chemotherapeutic and genic nanomedicine for the treatment of TNBC. The materials would have good application prospects in the field of clinical drug delivery.

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Section: Resultsmentioning

confidence: 99%

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

Wang,

Zhang,

et al. 2024

ACS Appl. Nano Mater.

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“…Эффективность применения указанных МАТ в терапии тяжёлого COVID-19 с развёрнутой клинической картиной ЦШ в большинстве опубликованных работ характеризуется как достаточно высокая [22][23][24]. Тем не менее, анализ уровня С-реактивного белка (СРБ) -основного биомаркера активности ИЛ-6выявил недостаточное ингибирование данного цитокина у пациентов, применявших анти-ИЛ-6 МАТ в стандартных дозах для терапии развёрнутой клинической картины ЦШ [25]. Опубликованные результаты указывают на то, что на фоне уже сформировавшихся высоких уровней ИЛ-6 в организме достаточно сложно обратить вспять комплекс патологических процессов, сопровождающих ЦШ [25].…”

Section: клиническая фармакология Clinical Pharmacologyunclassified

“…Тем не менее, анализ уровня С-реактивного белка (СРБ) -основного биомаркера активности ИЛ-6выявил недостаточное ингибирование данного цитокина у пациентов, применявших анти-ИЛ-6 МАТ в стандартных дозах для терапии развёрнутой клинической картины ЦШ [25]. Опубликованные результаты указывают на то, что на фоне уже сформировавшихся высоких уровней ИЛ-6 в организме достаточно сложно обратить вспять комплекс патологических процессов, сопровождающих ЦШ [25]. В частности, это может быть связано с аккумуляцией части ИЛ-6 в организме в виде комплекса с растворимым рецептором, что обеспечивает длительное циркулирование данного цитокина и пролонгацию его эффектов.…”

Section: клиническая фармакология Clinical Pharmacologyunclassified

Efficacy of interleukin-6 inhibitors as a tool for preventive anti-inflammatory therapy for COVID-19

Zyryanov,

Butranova,

Abramova

2024

GCP

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The novel coronavirus infection (COVID-19) is characterized by damage, along with the lungs, to many other vital organs and systems. The prevalence and severity of the resulting lesions are determined by the ability of the SARS-CoV-2 virus to cause excessive activation of the immune response, accompanied by changes in both cellular and humoral components. Among humoral disorders, the most significant is the hypersecretion of cytokines, including interleukins (IL), in particular IL-6 and IL1β. Elevated levels of IL-6 are one of the main predictors of severe COVID-19 and death. So, blocking the effects of this cytokine is of fundamental importance for improving the clinical outcomes of patients. Monoclonal antibodies against human interleukin-6 receptor or against IL-6 have been widely studied in patients with extremely severe COVID-19, and to a lesser extent in mild and moderate severity. Regardless of the severity, maximum effectiveness is achieved when these drugs are administered as early as possible, which made it possible to create such a tool as preventive anti-inflammatory therapy. Preventive prescription of IL-6 inhibitors may be useful not only for hospitalized inpatients, but also for outpatients. This review is aimed to assess the effectiveness of early use of IL-6 inhibitors both in hospitalized and ambulatory patients with varying degrees of severity of COVID-19.

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“…Mathematical modeling can help to optimize time schedules and sequential combinations of drugs. 151 Ultimately, drug tolerance and toxicity of the co-inhibitory treatment must be considered.…”

Section: Combination Therapies Including Il-6 Cytokine Family Blockadementioning

confidence: 99%

New perspectives in cancer immunotherapy: targeting IL-6 cytokine family

Soler,

Abaurrea,

Azcoaga

et al. 2023

J Immunother Cancer

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Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6 family, which includes IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1, have been shown to elicit tumor-promoting roles by modulating the TME, making them attractive therapeutic targets for cancer treatment.The development of immune checkpoint blockade (ICB) immunotherapies has radically changed the outcome of some cancers including melanoma, lung, and renal, although not without hurdles. However, ICB shows limited efficacy in other solid tumors. Recent reports support that chronic inflammation and IL-6 cytokine signaling are involved in resistance to immunotherapy. This review summarizes the available preclinical and clinical data regarding the implication of IL-6-related cytokines in regulating the immune TME and the response to ICB. Moreover, the potential clinical benefit of combining ICB with therapies targeting IL-6 cytokine members for cancer treatment is discussed.

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Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling

Cited by 6 publications

References 28 publications

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

Peptide-Modified Cyclodextrin-Based Nanosystem for Co-Delivery of Celastrol and siPD-L1 to Tumors

Efficacy of interleukin-6 inhibitors as a tool for preventive anti-inflammatory therapy for COVID-19

New perspectives in cancer immunotherapy: targeting IL-6 cytokine family

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