BCMA/CD47-directed universal CAR-T cells exhibit excellent antitumor activity in multiple myeloma

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 23, 2024

Abstract Background BCMA-directed autologous chimeric antigen receptor T (CAR-T) cells have shown excellent clinical efficacy in relapsed or refractory multiple myeloma (RRMM), however, the current preparation process for CAR-T is complicated and costly. Moreover, upregulation of CD47 expression has been observed myeloma, anti-CD47 antibodies remarkable results trials. Therefore, we focus on development BCMA/CD47-directed universal (UCAR-T) to improve these limitations. Methods In this study, employed phage display technology screen nanobodies against BCMA protein, determined characterization nanobodies. Furthermore, simultaneously disrupted endogenous TRAC B2M genes using CRISPR/Cas9 system generate TCR HLA double knock-out cells, developed UCAR-T detected antitumor activity vitro vivo. Results We obtained fourteen one specific protein from immunized VHH library, respectively. exhibited superior CAR (89.13-98.03%), effectively killing primary human MM cell lines. demonstrated prolonged survival tumor-engrafted NCG mice Conclusions This work that potent vivo, which provides a potential strategy novel “off-the-shelf” cellular immunotherapies treatment myeloma. Graphic

Язык: Английский

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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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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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