The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2719 - 2719

Опубликована: Март 8, 2021

Tumor necrosis factor alpha (TNF-α) was initially recognized as a that causes the of tumors, but it has been recently identified to have additional important functions pathological component autoimmune diseases. TNF-α binds two different receptors, which initiate signal transduction pathways. These pathways lead various cellular responses, including cell survival, differentiation, and proliferation. However, inappropriate or excessive activation signaling is associated with chronic inflammation can eventually development complications such Understanding mechanism expanded applied for treatment immune diseases, resulted in effective therapeutic tools, inhibitors. Currently, clinically approved inhibitors shown noticeable potency variety novel are being evaluated. In this review, we briefly introduce impact on diseases its inhibitors, used agents against

Язык: Английский

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Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

Cells, Год журнала: 2021, Номер 10(1), С. 111 - 111

Опубликована: Янв. 9, 2021

Cytokines are small proteins that secreted by a vast majority of cell types in the gut. They not only establish cell-to-cell interactions and facilitate cellular signaling, but also regulate both innate adaptive immune responses, thereby playing central role genetic, inflammatory, infectious diseases Both, cells gut epithelial cells, play important roles intestinal disease development. The epithelium is located between mucosal system microbiome. It establishes an efficient barrier against microbes, it signals information from lumen its composition to compartment. Communication across layer occurs other direction. Intestinal respond cytokines their response influences shapes microbial community within lumen. Thus, should be seen as translator or moderator microbiota system. Proper communication seems key homeostasis. Indeed, current genome-wide association studies for disorders have identified several susceptibility loci, which map cytokine signatures related signaling genes. A thorough understanding this tightly regulated network crucial. main objective review was shed light on how can orchestrate functions such proliferation, death, permeability, microbe interaction, maintenance, safeguarding host health. In addition, cytokine-mediated therapy inflammation cancer discussed.

Язык: Английский

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Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products

Journal of Clinical Medicine, Год журнала: 2020, Номер 9(5), С. 1273 - 1273

Опубликована: Апрель 28, 2020

Inflammatory bowel disease (IBD) is a chronic and life-long characterized by gastrointestinal tract inflammation. It caused the interplay of host’s genetic predisposition immune responses, various environmental factors. Despite many treatment options, there no cure for IBD. The increasing incidence prevalence IBD lack effective long-term options have resulted in substantial economic burden to healthcare system worldwide. Biologics targeting inflammatory cytokines initiated shift from symptomatic control towards objective goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved US Food Drug Administration induction maintenance clinical remission Adverse side effects associated with almost all currently available drugs, especially biologics, main challenge management. Natural products significant potential therapeutic agents an role health care. Given that natural display great structural diversity relatively easy modify chemically, they represent ideal scaffolds upon which generate novel therapeutics. This review focuses on pathology, challenges, roles played discusses these within current biodiscovery research agenda, including applications drug discovery techniques search next-generation drugs treat plethora diseases, major focus

Язык: Английский

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Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Journal of Immunology Research, Год журнала: 2019, Номер 2019, С. 1 - 19

Опубликована: Ноя. 25, 2019

Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH made clinically applying diagnostic scores; however, the heterotopic phenotype often makes rapid determination challenging. responds favorably to steroids pharmacologic immunosuppression, transplantation only necessary cases with acute failure or end-stage cirrhosis. Recurrence development de novo after possible, treatment similar standard therapy. Current experimental investigations T cell-mediated autoimmune pathways analysis changes within intestinal microbiome might advance our knowledge on pathogenesis trigger spark hope for novel therapeutic strategies.

Язык: Английский

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Ozoralizumab, a Humanized Anti-TNFα NANOBODY® Compound, Exhibits Efficacy Not Only at the Onset of Arthritis in a Human TNF Transgenic Mouse but Also During Secondary Failure of Administration of an Anti-TNFα IgG

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 22, 2022

Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in treatment rheumatoid arthritis (RA), traditional anti-TNFα antibodies are somewhat immunogenic, and their use results formation anti-drug (ADAs) loss efficacy (secondary failure). Ozoralizumab is trivalent, bispecific NANOBODY ® compound that differs structurally from IgGs. In this study we investigated suppressant effect ozoralizumab adalimumab, an IgG, on induction ADAs human TNF transgenic mice. markedly suppressed progression did not induce during long-term administration. We also developed animal model secondary failure by repeatedly administering adalimumab found switching to was followed superior anti-arthritis secondary-failure model. Moreover, form large immune complexes might lead ADA formation. The our studies suggest ozoralizumab, which exhibited low immunogenicity used has different antibody structure IgGs, promising candidate for RA patients only at onset but treatment.

Язык: Английский

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Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study

Journal of Crohn s and Colitis, Год журнала: 2022, Номер 16(9), С. 1436 - 1446

Опубликована: Апрель 7, 2022

Abstract Background Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of [CT-P13] has recently been shown to be as effective IV after two doses induction in randomised trial, but there are no data support elective switching patients on maintenance therapy. We aimed assess the effectiveness an programme SC CT-P13 treated with infliximab. Methods Patients established infliximab, who switched CT-P13, were included this retrospective multicentre cohort study. Disease activity was monitored serially Harvey-Bradshaw Index [HBI] Crohn’s disease [CD] and Simple Clinical Colitis Activity [SCCAI] ulcerative colitis (UC) up 12 months at 3, 6, 12. Faecal calprotectin [FC] C-reactive protein [CRP] recorded baseline follow-up, if available. Infliximab trough levels measured prior switch following switch. The primary outcome measure treatment persistence latest follow-up. Secondary measures pharmacokinetics [PK], safety, need corticosteroid rescue therapy, surgery. Results 181 patients, whom 115 [63.5%] had CD. majority [72.4%] 8-weekly dosing intravenous switching, more than half [59.1%] concomitant immunomodulatory (CD: 106, 92.2%; UC: 46, 76.7%; IBD unclassified [IBD-U]: 5, 83.3%) clinical remission. Treatment rate high [n = 167, 92.3%] only 14 [7.7%] stopped during follow-up period. There significant difference between repeat measurements or HBI, SCCAI, CRP, FC. Of total cohort, 25 (13.8%) perianal these, [8%] worsening CD required antibiotic further examination under anaesthesia [EUA]. Both these also back Median level increased from 8.9 µg/dl [range 0.4-16] 16.0 2.3-16, p <0.001] 3 months. Serum stayed stable 6 [median 16 µg/dl, range 0.3-17.2] 0.3-19.1, both <0.001 compared baseline]. Among variables examined, antibodies [ATI] associated (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, <0.001]. developed ATI; nine [64.3%] Immunomodulatory not significantly development ATI [p 0.15]. In subset receiving escalated frequency observed weekly versus alternate CT-P13. Patient acceptance satisfaction rates very high. Conclusions we low immunogenicity, change indices biomarkers. serum levels.

Язык: Английский

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Sequential immunotherapy: towards cures for autoimmunity

Nature Reviews Drug Discovery, Год журнала: 2024, Номер 23(7), С. 501 - 524

Опубликована: Июнь 5, 2024

Язык: Английский

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Emerging strategies for nanomedicine in autoimmunity

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115194 - 115194

Опубликована: Фев. 10, 2024

Язык: Английский

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Therapeutic drug monitoring and neutralizing anti-drug antibody detection to optimize TNF-alpha inhibitor treatment for uveitis

Frontiers in Ophthalmology, Год журнала: 2025, Номер 5

Опубликована: Янв. 28, 2025

Background Adalimumab taken every other week is an effective treatment in patients with chronic refractory uveitis. Patients who have a suboptimal response to this may suffer from recurrent inflammation and vision loss. Here, we investigated the use of therapeutic drug monitoring neutralizing anti-drug antibody detection as strategy optimize tumor necrosis factor (TNF)-alpha inhibitor initial dosing adalimumab. Method Retrospective cohort study performed two tertiary referral uveitis services United States between 2015 2023. non-infectious had two-week adalimumab underwent serum level reflex testing were followed. considered antibodies when levels low (less than or equal 6 mcg/mL) anti-adalimumab present on testing. Treatment adjustment was made by clinicians knowledge presence absence antibodies. Every either escalated weekly switched infliximab, alternate TNF-alpha inhibitor, based these findings. The primary outcome success failure at 12 months, determined disease inactivity steroid-sparing therapy. Results 32 included. 31.2% (n=10) found All medication switch infliximab remission rate 40% months. without (n=22) dose escalation (77.3%; n=17) (22.7%; n=5) achieved 68.2% Altogether, detection, our cohort, resulted 62.5%. Conclusions For experiencing dosed weeks, help treatment.

Язык: Английский

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Phage Display Technology as a Powerful Platform for Antibody Drug Discovery

Viruses, Год журнала: 2021, Номер 13(2), С. 178 - 178

Опубликована: Янв. 25, 2021

Antibody drugs with a high affinity and specificity are effective safe for intractable diseases, such as cancers autoimmune diseases. Furthermore, they have played central role in drug discovery, currently accounting eight of the top 20 pharmaceutical products worldwide by sales. Forty years ago, clinical trials on antibody that were thought to be magic bullet failed, partly due immunogenicity monoclonal antibodies produced mice. The recent breakthrough is largely because contribution phage display technology. Here, we reviewed importance technology powerful platform discovery from various perspectives, development human antibodies, enhancement identification therapeutic targets drugs.

Язык: Английский

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