Promising therapies for the treatment of myasthenia gravis DOI
Sanem Pınar Uysal, John A. Morren

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(4), P. 395 - 408

Published: March 3, 2024

Introduction Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with symptoms of varying severity and significant morbidity. The mainstay treatment in MG mitigation immune cascade steroids non-steroidal immunosuppressive therapies. therapeutic strategies are transitioning from broad indiscriminate immunosuppression to novel agents key steps pathogenesis, including T cell activation, B proliferation, complement maintenance pathogenic antibody production, proinflammatory cytokine production.

Language: Английский

The present and future of bispecific antibodies for cancer therapy DOI
Christian Klein, Ulrich Brinkmann, Janice M. Reichert

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(4), P. 301 - 319

Published: March 6, 2024

Language: Английский

Citations

138
Extracellular targeted protein degradation: an emerging modality for drug discovery DOI
James A. Wells, Kaan Kumru

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(2), P. 126 - 140

Published: Dec. 7, 2023

Language: Английский

Citations

67
Engineering the IL‐4/IL‐13 axis for targeted immune modulation DOI Creative Commons
Zachary J. Bernstein,

Anjali Shenoy,

Amy Chen

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 320(1), P. 29 - 57

Published: June 7, 2023

The structurally and functionally related interleukin-4 (IL-4) IL-13 cytokines play pivotal roles in shaping immune activity. IL-4/IL-13 axis is best known for its critical role T helper 2 (Th2) cell-mediated Type inflammation, which protects the host from large multicellular pathogens, such as parasitic helminth worms, regulates responses to allergens. In addition, IL-4 stimulate a wide range of innate adaptive cells, well non-hematopoietic coordinate various functions, including regulation, antibody production, fibrosis. Due importance broad spectrum physiological activities, network has been targeted through variety molecular engineering synthetic biology approaches modulate behavior develop novel therapeutics. Here, we review ongoing efforts manipulate axis, cytokine strategies, formulation fusion proteins, antagonist development, cell approaches, biosensor design. We discuss how these strategies have employed dissect pathways, discover new immunotherapies targeting allergy, autoimmune diseases, cancer. Looking ahead, emerging bioengineering tools promise continue advancing fundamental understanding enabling researchers exploit insights effective interventions.

Language: Английский

Citations

45
Myasthenia gravis: the changing treatment landscape in the era of molecular therapies DOI
Raffaele Iorio

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(2), P. 84 - 98

Published: Jan. 8, 2024

Language: Английский

Citations

36
Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties DOI Creative Commons
Nilufer P. Seth, Rui Xu,

Matthew DuPrie

et al.

mAbs, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 12, 2025

Nipocalimab is a human immunoglobulin G (IgG)1 monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high specificity and affinity at both neutral (extracellular) acidic (intracellular) pH, resulting in reduction of circulating IgG levels, including those pathogenic antibodies. Here, we present molecular, cellular, nonclinical characteristics nipocalimab support reported clinical pharmacology potential application IgG-driven, autoantibody- alloantibody-mediated diseases. The crystal structure antigen binding fragment (Fab)/FcRn complex reveals its unique epitope on site FcRn supports observed pH-independent high-binding FcRn. Cell-based vivo studies demonstrate concentration/dose- time-dependent occupancy reduction. selectively reduces levels without detectable effects other adaptive innate immune functions. In vitro experiments mice cynomolgus monkeys generated data align observations from

Language: Английский

Citations

3
Successful treatment with efgartigimod as an add-on therapy for acute attack of anti-NMDA receptor encephalitis: a case report DOI Creative Commons

Huasheng Huang,

Yizhi Wei,

HuiHui Qin

et al.

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 22, 2025

Anti-NMDA receptor encephalitis is an autoimmune, antibody-mediated inflammatory disease of the brain characterized by presence IgG antibodies targeting excitatory N-methyl-D-aspartate (NMDAR). Previous research has established that neonatal Fc (FcRn) regulates transport and circulation immunoglobulins (IgG). Efgartigimod, FcRn antagonist, been shown to enhance patient outcomes promoting clearance, it exhibited substantial clinical efficacy tolerability in treatment myasthenia gravis. Efgartigimod demonstrated potential various IgG-mediated autoimmune diseases. Nonetheless, date, no studies have investigated use efgartigimod anti-NMDAR encephalitis. We present a case 42-year-old male diagnosed with encephalitis, initially treated intravenous methylprednisolone(IVMP) human immunoglobulin (IVIG) without improvement. Subsequent administration resulted rapid improvement; however, experienced relapse upon discontinuation efgartigimod. Reintroduction led significant improvement, accompanied marked decrease serum levels both cerebrospinal fluid. The remained relapse-free during 2-month follow-up period. This demonstrates potentially effective therapy for acute phase

Language: Английский

Citations

2
Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain DOI Creative Commons
Nathan T. Fiore,

Kendal F. Willcox,

Dorsa Dayani

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Subcutaneous efgartigimod PH20 in generalized myasthenia gravis: A phase 3 randomized noninferiority study (ADAPT-SC) and interim analyses of a long-term open-label extension study (ADAPT-SC+) DOI Creative Commons
James F. Howard, Tuan Vu, George Li

et al.

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(5), P. e00378 - e00378

Published: Sept. 1, 2024

Language: Английский

Citations

14
Batoclimab vs Placebo for Generalized Myasthenia Gravis DOI
Chong Yan,

Yao-Xian Yue,

Yuzhou Guan

et al.

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(4), P. 336 - 336

Published: March 4, 2024

Importance Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in circulation alleviate symptoms patients with generalized MG. Objective To examine efficacy safety profile of batoclimab, a monoclonal IgG1 antibody, Design, Setting, Participants This was multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers China. Adult 18 years or older MG were screened, those who antibody positive enrolled. Intervention Eligible received batoclimab matching placebo addition standard care. Each treatment cycle consisted 6 weekly subcutaneous injections 680 mg, followed 4 weeks observation. A second required continuing treatment. Main Outcome Measure primary outcome sustained improvement, as defined 3-point greater reduction Gravis Activities Daily Living (MG-ADL) score baseline for more consecutive first individuals acetylcholine muscle-specific kinase antibodies. Results total 178 adult 132 randomly assigned, 131 tested antibodies, 1 negative (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) rate MG-ADL improvement antibody-positive 31.3% (20 64) group vs 58.2% (39 67) (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). diverged between 2 groups early week 2. mean (SE) maximum difference occurred after last dose (day 43, 1.7 [0.3] 3.6 group; difference, −1.9; −2.8 −1.0; nominal < rates treatment-related severe treatment-emergent adverse events 36.9% (24 65) 7.7% (5 70.1% (47 3.0% (2 group, respectively. Conclusions Relevance Batoclimab increased well tolerated Clinical effects extent IgG similar previously reported rozanolixizumab. Future studies large sample size are needed further understand batoclimab. Trial Registration ClinicalTrials.gov Identifier: NCT05039190

Language: Английский

Citations

13
Structure and function of therapeutic antibodies approved by the US FDA in 2023 DOI Creative Commons
William R. Strohl

Antibody Therapeutics, Journal Year: 2024, Volume and Issue: 7(2), P. 132 - 156

Published: March 15, 2024

In calendar year 2023, the United States Food and Drug Administration (US FDA) approved a total of 55 new molecular entities, which 12 were in class therapeutic antibodies. Besides antibody protein drugs, US FDA also another five non-antibody making broader drugs about 31% drugs. Among antibodies by FDA, 8 relatively standard IgG formats, 3 bivalent, bispecific 1 was trivalent, antibody. no antibody-drug conjugates, immunocytokines or chimeric antigen receptor-T cells approved. Of antibodies, two targeted programmed cell death receptor-1 (PD-1) for orphan indications, CD20 diffuse large B lymphoma, different receptors (B-cell maturation [BCMA] G-coupled receptor C, group 5, member D [GPRC5D]) treatment multiple myeloma, one each that amyloid-β protofibrils Alzheimer's disease, neonatal Fc alpha-chain myasthenia gravis, complement factor C5 CD55 deficiency with hyper-activation complement, angiopathic thrombosis severe protein-losing enteropathy interleukin (IL)-23p19 severely active ulcerative colitis, IL-17A-F plaque psoriasis respiratory syncytial virus (RSV)-F season-long RSV prophylaxis infants.

Language: Английский

Citations

9