Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(4), С. 1630 - 1630

Опубликована: Фев. 17, 2023

Due to the key role of tumor necrosis factor-alpha (TNF-α) in pathogenesis immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used clinical treatment autoimmune disorders. Currently, five anti-TNF-α drugs approved: infliximab, adalimumab, golimumab, certolizumab pegol etanercept. Anti-TNF-α biosimilars are also available for use. Here, we will review historical development as well present potential future applications therapies, which led major improvements patients with several such rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) chronic endogenous uveitis. Other therapeutic areas under evaluation, including viral infections, e.g., COVID-19, neuropsychiatric disorders certain forms cancer. The search biomarkers able predict responsiveness is discussed.

Язык: Английский

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The role of inflammation in autoimmune disease: a therapeutic target

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 4, 2023

Autoimmune diseases (AIDs) are immune disorders whose incidence and prevalence increasing year by year. AIDs produced the system’s misidentification of self-antigens, seemingly caused excessive function, but in fact they result reduced accuracy due to decline system which cannot clearly identify foreign invaders thus issuing false attacks, eventually leading disease. The occurrence is often accompanied emergence inflammation, inflammatory mediators (inflammatory factors, inflammasomes) play an important role pathogenesis AIDs, mediate process affecting innate cells (such as macrophages) adaptive T B cells), ultimately promote autoimmune responses, so targeting mediators/pathways one emerging treatment strategies AIDs. This review will briefly describe inflammation different give a rough introduction inhibitors hoping have reference significance for subsequent options

Язык: Английский

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TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 6, 2023

Pancreatic cancer is a highly aggressive malignancy with limited treatment options and poor prognosis. Trophoblast cell surface antigen 2 (TROP2), overexpressed in the tumors of more than half pancreatic patients, has been identified as potential target for antibody-drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are IgG type have poorly studied cancer. Here, we aimed to develop novel nanobody-drug conjugate (NDC) targeting TROP2 cancer.In this study, developed NDC, HuNbTROP2-HSA-MMAE, TROP2-positive HuNbTROP2-HSA-MMAE characterized by use nanobodies against human serum albumin (HSA) drug-antibody ratio 1. exhibited specific binding was internalized into tumor cells high endocytosis efficiency within 5 h, followed intracellular translocation lysosomes release MMAE induce apoptosis through caspase-3/9 pathway. In xenograft model cancer, doses 0.2 mg/kg 1 demonstrated significant antitumor effects, dose even eradicated tumor.HuNbTROP2-HSA-MMAE desirable affinity, internalization activity. It holds promise therapeutic option

Язык: Английский

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TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond

Nature Reviews Rheumatology, Год журнала: 2023, Номер 19(9), С. 576 - 591

Опубликована: Авг. 4, 2023

Язык: Английский

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A pivotal decade for bispecific antibodies?

mAbs, Год журнала: 2024, Номер 16(1)

Опубликована: Март 11, 2024

Bispecific antibodies (bsAbs) are a class of that can mediate novel mechanisms action compared to monospecific monoclonal (mAbs). Since the discovery mAbs and their adoption as therapeutic agents in 1980s 1990s, development bsAbs has held substantial appeal. Nevertheless, only three (catumaxomab, blinatumomab, emicizumab) were approved through end 2020. However, since then, 11 received regulatory agency approvals, which nine (amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) for treatment cancer two (faricimab, ozoralizumab) non-oncology indications. Notably, 13 currently bsAbs, two, emicizumab faricimab, have achieved blockbuster status, showing promise this therapeutics. In 2020s, approval additional be expected hematological malignancies, solid tumors indications, establishing essential part armamentarium.

Язык: Английский

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Camelid Single-Domain Antibodies: Promises and Challenges as Lifesaving Treatments

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 5009 - 5009

Опубликована: Апрель 30, 2022

Since the discovery of camelid heavy-chain antibodies in 1993, there has been tremendous excitement for these antibody domains (VHHs/sdAbs/nanobodies) as research tools, diagnostics, and therapeutics. Commercially, several patents were granted to pioneering groups Belgium Netherlands between 1996–2001. Ablynx was established 2001 with aim exploring therapeutic applications development nanobody drugs. Extensive efforts over two decades at led first approved drug, caplacizumab (Cablivi) by EMA FDA (2018–2019) treatment rare blood clotting disorders adults acquired thrombotic thrombocytopenic purpura (TPP). The relatively long time sdAb their entry into market reflects novelty approach, together intellectual property restrictions freedom-to-operate issues. approval expiration key patents, may open a new horizon emergence sdAbs mainstream biotherapeutics years come. It remains be seen if nanobody-based drugs will cheaper than traditional antibodies. In this review, I provide critical perspectives on present promises challenges widespread adoption diagnostic agents.

Язык: Английский

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Ozoralizumab: First Approval

Drugs, Год журнала: 2022, Номер 83(1), С. 87 - 92

Опубликована: Дек. 13, 2022

Язык: Английский

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Phase II/III Results of a Trial of Anti–Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients With Rheumatoid Arthritis

Arthritis & Rheumatology, Год журнала: 2022, Номер 74(11), С. 1776 - 1785

Опубликована: Июнь 22, 2022

To assess the efficacy and safety of subcutaneous administration 30 mg or 80 ozoralizumab plus methotrexate (MTX) in patients with rheumatoid arthritis (RA) whose disease remained active despite MTX therapy.In this multicenter, double-blind, parallel-group, placebo-controlled phase II/III trial, 381 were randomized to receive placebo, mg, subcutaneously injected every 4 weeks for 24 weeks. The primary end points response rates based on American College Rheumatology 20% improvement criteria (ACR20) at week 16 change Sharp/van der Heijde score (ΔSHS) from baseline 24.The proportion an ACR20 was significantly higher (P < 0.001) both groups (79.6% 75.3% mg), compared placebo (37.3%); these improvements observed first treatment. structural nonprogression (ΔSHS ≤0) than group. For some secondary points, greater starting as early day 3. Serious adverse events occurred 30-mg group 5 80-mg group.In RA who received combination MTX, signs symptoms reduced outcomes those receiving placebo. Ozoralizumab demonstrated acceptable tolerability no new signals when other antibodies against tumor necrosis factor.

Язык: Английский

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Design and engineering of bispecific antibodies: insights and practical considerations

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Янв. 25, 2024

Bispecific antibodies (bsAbs) have attracted significant attention due to their dual binding activity, which permits simultaneous targeting of antigens and synergistic effects beyond what can be obtained even with combinations conventional monospecific antibodies. Despite the tremendous therapeutic potential, design construction bsAbs are often hampered by practical issues arising from increased structural complexity as compared The diverse in nature, spanning decreased biophysical stability fusion exogenous antigen-binding domains antibody chain mispairing leading formation antibody-related impurities that very difficult remove. added requires judicious considerations well extensive molecular engineering ensure high quality intended mode action favorable drug-like qualities. In this review, we highlight summarize some key state-of-the-art principles applied efficient formats.

Язык: Английский

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Effect of Ozoralizumab Administration with or without Methotrexate in Patients with Rheumatoid Arthritis: A Post-Hoc Analysis

Rheumatology and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Язык: Английский

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