Novel therapeutic strategies for autoimmune and inflammatory rheumatic diseases

Felten, Renaud; Mertz, Philippe; Sebbag, E.; Scherlinger, Marc; Arnaud, Laurent

doi:10.1016/j.drudis.2023.103612

Cited by 9 publications

(7 citation statements)

References 70 publications

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“…Experience in this setting is summarized in the Supplementary Tables S1–S3 . 2 , 43 To ensure RMD patient eligibility to innovative CTs and fitness, the indications, contraindications and disease-specific assessments in Table 2 A and B should be considered. This list is not exhaustive, and, in the trial setting, trial protocols should be followed.…”

Section: Results (Consensus Recommendations)mentioning

confidence: 99%

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Greco,

Alexander,

Del Papa

et al. 2024

eClinicalMedicine

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Section: Results (Consensus Recommendations)mentioning

confidence: 99%

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Greco,

Alexander,

Del Papa

et al. 2024

eClinicalMedicine

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“…30 In recent years, novel therapeutic modalities such as combination of targeted therapies, bispecific monoclonal antibodies (mAbs), stem cell therapy, therapeutic vaccines, and chimeric antigen receptor (CAR)-T cells have emerged, significantly augmenting the treatment outcomes for patients. 31 However, owing to the inherent heterogeneity of SADs, a subset of patients still demonstrated suboptimal response rates while necessitating prolonged follow-up periods to identify potential adverse effects associated with new treatments. 32,33 SADs can be triggered or induced by internal and external factors, and a better understanding of the etiology and pathogenesis may be helpful for diagnoses, disease activity prediction, and individual treatment.…”

Section: Discussionmentioning

confidence: 99%

“…SADs are characterized by self‐antibody production and immune imbalance, leading to inflammatory reactions and damage of multiple tissues 30 . In recent years, novel therapeutic modalities such as combination of targeted therapies, bispecific monoclonal antibodies (mAbs), stem cell therapy, therapeutic vaccines, and chimeric antigen receptor (CAR)‐T cells have emerged, significantly augmenting the treatment outcomes for patients 31 . However, owing to the inherent heterogeneity of SADs, a subset of patients still demonstrated suboptimal response rates while necessitating prolonged follow‐up periods to identify potential adverse effects associated with new treatments 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of serum Epstein–Barr virus envelope glycoproteins antibodies and their association with systemic autoimmune diseases

Li,

Zhong,

Kang

et al. 2024

Journal of Medical Virology

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Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein–Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein–Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross‐reactivity between gp350 antibodies and SADs‐associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.

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“…In some autoimmune diseases, BsAbs play a therapeutic role in preventing immune contacts by neutralizing inflammatory cytokines or focusing on surface indicators between activated T cells and B lymphocytes or antigenic presenting cells. 28 BsAbs are currently categorized into three major structural classes: antibody fragments, or alternative scaffold proteins fused to an immunoglobulin Fc region or to proteins that increase their pharmacokinetic properties and valency (e.g. DVD-Igs and IgG-scFvs), and recombinant IgG BsAbs that maintain the structure of native IgGs.…”

Section: Schematic Illustration Of Engineering a Bispecific Nanobody-...mentioning

confidence: 99%

“…However, the potential of BsAb in IBD clinical applications to enhance therapeutic efficacy is foreseeable. In some autoimmune diseases, BsAbs play a therapeutic role in preventing immune contacts by neutralizing inflammatory cytokines or focusing on surface indicators between activated T cells and B lymphocytes or antigenic presenting cells 28 …”

Section: Introductionmentioning

confidence: 99%

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

Wang,

Kang,

et al. 2024

Clinical & Translational Med

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BackgroundInflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non‐response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF‐α (tumour necrosis factor‐α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond.MethodsWe designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage‐expressed membrane TNF‐α (hmTNF‐α) and IL‐23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb‐Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb‐Fc.ResultsBsNb‐Fc exhibited an improved serum half‐life, targeting capability and effector function than BsNb. It's demonstrated that BsNb‐Fc exhibited superior anti‐inflammatory effects compared to the anti‐TNF‐α mAb (infliximab, IFX) combined with anti‐IL‐12/IL‐23p40 mAb (ustekinumab, UST) by Transwell co‐culture assays. Notably, in murine models of acute colitis brought on by 2,4,6‐trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb‐Fc effectively alleviated colitis severity. Additionally, BsNb‐Fc outperformed the IFX&UST combination in TNBS‐induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS.ConclusionThese findings highlight an enhanced efficacy and improved biostability of BsNb‐Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF‐α inhibition.Key points A bispecific nanobody (BsNb) was created to target TNF‐α and IL‐23p19, exhibiting high affinity and remarkable stability. BsNb‐Fc inhibited the release of cytokines in CD4+T cells during co‐culture experiments. BsNb‐Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

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Novel therapeutic strategies for autoimmune and inflammatory rheumatic diseases

Cited by 9 publications

References 70 publications

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee

Evaluation of serum Epstein–Barr virus envelope glycoproteins antibodies and their association with systemic autoimmune diseases

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

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