A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Окт. 27, 2022

Abstract In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high efficacy shortly after subcutaneous injection. To elucidate mechanism underlying rapid onset of effects ozoralizumab, we compared biodistribution kinetics and adalimumab injection in an animal model arthritis. Alexa Fluor 680-labeled were administered by once (2 mg/kg) at five weeks induction collagen-induced arthritis (CIA) model. The time-course changes fluorescence intensities two compounds paws serum evaluated. CIA mice harvested four eight hours for microscopy. Biofluorescence imaging revealed better distribution to joint tissues than adalimumab, as early Fluorescence microscopy a greater intensity that Ozoralizumab significantly higher absorption rate constant with adalimumab. These results indicate enters systemic circulation more rapidly is distributed target earlier levels conventional IgG antibodies. Our investigation provides new insight into practice.

Язык: Английский

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Unique structure of ozoralizumab, a trivalent anti-TNFα NANOBODY® compound, offers the potential advantage of mitigating the risk of immune complex-induced inflammation

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 14, 2023

Biologics have become an important component of treatment strategies for a variety diseases, but the immunogenicity large immune complexes (ICs) and aggregates biologics may increase risk adverse events is concern it remains unclear whether ICs consisting intrinsic antigen therapeutic antibodies are actually involved in acute local inflammation such as injection site reaction (ISR). Ozoralizumab trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. Treatment with ozoralizumab has been shown to provide beneficial effects rheumatoid arthritis (RA) comparable those obtained other TNFα inhibitors. Very few ISRs (2%) reported after administration, drug acceptable safety tolerability. In this study, order elucidate mechanism underlying reduced incidence associated we investigated stoichiometry two inhibitors (ozoralizumab adalimumab, anti-TNFα IgG) induction by these drugs Fcγ receptor (FcγR)-mediated responses on neutrophils. Ozoralizumab-TNFα smaller than adalimumab-TNFα lack Fc portion, thus mitigating FcγR-mediated We also developed model antibody-TNFα IC-induced subcutaneous found ozoralizumab-TNFα do not induce any significant at sites. The results our studies suggest promising candidate RA entails lower IC-mediated cell activation leads unwanted responses.

Язык: Английский

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Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review

Molecular Pharmaceutics, Год журнала: 2023, Номер 20(11), С. 5345 - 5358

Опубликована: Окт. 23, 2023

An endogenous transporter protein called albumin interacts with the Fc receptor to provide it multiple substrate-binding domains, cell membrane activation, and an extended circulating half-life. Albumin has remarkable ability bind receptors viz. secreted acidic rich in cysteine (SPARC) scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of disease site instead requiring specialized substrates be added nanocarrier. RA, a chronic autoimmune illness, is characterized by presence severe inflammatory response. RA patients have low serum concentration, which signifies high uptake at sites, giving rationale use as drug carrier for therapy. capacity both passive targeting. It abundantly available bloodstream showing excellent cellular compatibility, degradability biological tissues, nonantigenicity, safety. There three strategies mediated delivery encapsulating therapeutics nanoparticles, chemically conjugating drugs functional proteins, itself used ligand deliver specifically cells or tissues express albumin-binding receptors. In current review, attempt been made highlight significant evidence safe effective management RA. Evidence provided form recent research advances, clinical trials, patents. Additionally, this review will outline prospective potential utilization vehicle suggest possible future avenues perspective subsequent studies.

Язык: Английский

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Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

Cancers, Год журнала: 2024, Номер 16(15), С. 2681 - 2681

Опубликована: Июль 27, 2024

Background: Antibody–drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due acquired resistance potential side Objectives: This study focuses on advances in various ADC components improve both the efficacy safety of these agents, includes analysis several novel formats. work assesses whether unique features VHHs—such as small size, enhanced tissue penetration, stability, cost-effectiveness—make them a viable alternative conventional antibodies reviews current status development. Methods: Following PRISMA guidelines, this focused VHHs ADCs, examining advancements prospects from 1 January 2014 30 June 2024. Searches were conducted PubMed, Cochrane Library, ScienceDirect LILACS using specific terms related single-domain antibodies. Retrieved articles rigorously evaluated, excluding duplicates non-qualifying studies. The selected peer-reviewed analyzed quality synthesized highlight advancements, methods, payloads, future directions research. Results: offer significant advantages drug conjugation over smaller size structure, which enhance penetration enable access previously inaccessible epitopes. Their superior solubility, manufacturability facilitate cost-effective production expand range targetable antigens. Additionally, some naturally cross blood–brain barrier or be easily modified favor making promising targeting brain tumors metastases. Although no VHH–drug (nADC nanoADC) are currently clinical arena, preclinical studies have explored methods linkers. Conclusions: While transforming treatment, mechanisms associated toxicities challenge traditional views bioavailability vary with different types. Severe toxicities, often linked compound instability, effects, nonspecific blood cell interactions, need better understanding. Conversely, rapid distribution, clearance could advantageous, potentially toxicity by minimizing prolonged exposure. These attributes make strong candidates next generation enhancing safety.

Язык: Английский

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Promises and challenges of single-domain antibodies to control influenza

Antiviral Research, Год журнала: 2024, Номер 222, С. 105807 - 105807

Опубликована: Янв. 13, 2024

Язык: Английский

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