BioDrugs最新文献

{"title":"Incidence and Risk Factors of Treatment-Emergent Eczematous Reactions in Patients with Psoriasis Treated with Biologics: A Systematic Review and Meta-Analysis.","authors":"Yifei Feng, Yan Lu","doi":"10.1007/s40259-026-00809-6","DOIUrl":"https://doi.org/10.1007/s40259-026-00809-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Treatment-emergent eczematous reactions have been reported in patients with psoriasis receiving biologic therapies, but their pooled incidence and associated factors remain unclear. We aimed to estimate the incidence and associated factors for treatment-emergent eczematous reactions in biologic-treated psoriasis patients.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, and Web of Science (to Jan 2026) for studies reporting new-onset or exacerbated eczema in psoriasis patients treated with tumor necrosis factor (TNF), interleukin-17 (IL-17), interleukin-12/23 (IL-12/23), or IL-23 inhibitors. Two eligible studies of the oral tyrosine kinase 2 (TYK2) inhibitor deucravacitinib were analyzed separately as an exploratory subgroup. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, data were synthesized using a random-effects model with Freeman-Tukey double arcsine transformation. The primary outcome was the pooled incidence of treatment-emergent eczematous reactions. Secondary analyses examined differences according to biologic class, dosage, and demographic characteristics.</p><p><strong>Results: </strong>Analysis of 26 publications (34,511 exposures) showed a 2.17% overall incidence (95% CI 1.57-2.85). Pooled incidence differed by class (p < 0.001): IL-17 inhibitors had the highest incidence (3.47%; 95% CI 2.34-4.77), followed by IL-12/23 (2.15%; 95% CI 0.04-6.59) and TNF inhibitors (1.02%; 95% CI 0.83-1.23), and IL-23 inhibitors had the lowest (0.09%; 95% CI 0.00-0.71). Within the IL-17 class, pooled incidence was higher with secukinumab (5.3%; 95% CI 2.95-8.2) than with ixekizumab (1.51%; 95% CI 0.41-3.1). High-dose regimens were associated with a higher pooled incidence than low-dose regimens (7.65% vs 3.36%; p = 0.03). Incidence was higher in studies conducted in East Asian populations (~ 6%) than in Western populations (~ 1%). A history of atopic dermatitis showed the strongest patient-level association with treatment-emergent eczematous reactions (hazard ratio, 12.40; 95% CI 6.97-22.06).</p><p><strong>Conclusions: </strong>Eczematous reactions in biologic-treated psoriasis were associated with biologic class, dose, and study population, with the highest incidences for IL-17 inhibitors, high-dose regimens, and studies of East Asian populations.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Reflection to Implementation: Tailored Clinical Development of a Pembrolizumab Biosimilar Candidate.","authors":"Björn Capsius, Marija Pesic, Ravil Niyazov, Susanne Pippig, Michael Trieb, Rahul Hole, Sigrid Balser, Andreas Seidl","doi":"10.1007/s40259-026-00803-y","DOIUrl":"https://doi.org/10.1007/s40259-026-00803-y","url":null,"abstract":"<p><p>Regulatory science increasingly recognizes that comparative efficacy studies may provide limited additional certainty to biosimilar development when high-resolution analytical, functional, and pharmacokinetic data robustly demonstrate similarity to the reference product. Modern structural and functional assays, combined with sensitive pharmacokinetic studies are capable of detecting differences with greater sensitivity than clinical efficacy endpoints. Accordingly, recent European Medicines Agency, US Food and Drug Administration, Medicines and Healthcare products Regulatory Agency, and Health Canada guidance suggest increasing alignment toward a \"fit-for-purpose\" pharmacokinetic-anchored clinical approach for biologics with well-characterizable structure and function. Pembrolizumab biosimilar development represents an early real‑world implementation of a streamlined clinical development approach. Its mechanism of action is well understood and driven by programmed cell death protein 1 (PD-1) receptor blockade with minimal reliance on fragment crystallizable-mediated effector functions, and its analytical traceability enables a detailed structure-function characterization. For this molecule, comparative pharmacokinetics provides a sensitive clinical measure of similarity that may be assessed in a multiple-dose pharmacokinetic equivalence study conducted in a sensitive patient population receiving adjuvant treatment following tumor resection. The comparative pharmacokinetic study design also provides a scientifically justified framework to assess safety and immunogenicity. In the development program of the pembrolizumab biosimilar candidate FYB206, scientific reasoning is used to illustrate how tailored pharmacokinetic-centered programs can maintain scientific rigor while reducing unnecessary clinical burden. More broadly, this approach may be considered applicable to other biologics with a well-defined mechanism of action, robust analytical accessibility, and sensitive functional assays, enabling scientifically proportionate and efficient biosimilar development. As FYB206 has not yet received regulatory approval; considerations presented herein reflect a forward‑looking scientific perspective based on the totality of available evidence.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-Based Systems for Producing Therapeutic Proteins: Current Status and Future Prospects.","authors":"Qiang Chen","doi":"10.1007/s40259-026-00811-y","DOIUrl":"10.1007/s40259-026-00811-y","url":null,"abstract":"<p><p>Protein-based therapeutics have transformed modern disease treatment and now constitute a rapidly expanding segment of the pharmaceutical market. In this context, plant-based expression systems have emerged as a versatile alternative to conventional mammalian cell platforms for the production of recombinant proteins. Beyond their well-established advantages in cost, scalability, and biosafety, recent advances in transient expression technologies and plant cell culture systems have enabled rapid, high-yield production of complex biologics with increasing control over product quality. In particular, deconstructed viral vectors and Agrobacterium-mediated transient expression in plants enable rapid recombinant protein production, supporting their potential for applications requiring flexible and accelerated manufacturing. Concurrently, progress in host glycoengineering has enabled the generation of humanized and functionally tailored glycoforms, including antibody glycovariants with enhanced Fc-mediated effector functions. These advances have expanded the applicability of plant-based platforms to the production of monoclonal antibodies, antibody fragments, and emerging antibody-based modalities. In parallel, a broad range of single-chain therapeutic proteins, including enzymes, antimicrobial and antiviral agents, and proteins for inducing immune tolerance, have been successfully produced in plant systems as biologically active and functional therapeutics, demonstrating the broad utility of plant-based platforms across multiple therapeutic classes. This review provides a comprehensive overview of current plant-based production platforms, including whole-plant and plant cell suspension systems, and evaluates their comparative advantages and limitations relative to mammalian expression technologies. Recent progress in the development of therapeutic proteins, with an emphasis on monoclonal antibodies for passive immunization, is highlighted. Finally, the remaining technical, regulatory, and commercial challenges are discussed, along with future prospects for integrating plant-based systems into mainstream biopharmaceutical manufacturing.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLX11: A Pertuzumab Biosimilar.","authors":"Aisling McGuigan","doi":"10.1007/s40259-026-00807-8","DOIUrl":"https://doi.org/10.1007/s40259-026-00807-8","url":null,"abstract":"<p><p>HLX11 (pertuzumab-dpzb in the USA), marketed as POHERDY^® in the USA and EU and as HANBEIYOU^® in China, is a biosimilar of reference pertuzumab, an anti-human epidermal growth factor 2 (HER2) monoclonal antibody. It is approved for use in the same indications as reference pertuzumab: early or metastatic HER2-positive breast cancer. The physicochemical and functional properties of HLX11 are similar to reference pertuzumab, and pharmacokinetic equivalence has been shown in healthy individuals. HLX11 demonstrated equivalent clinical efficacy to EU-sourced reference pertuzumab in the neoadjuvant treatment of patients with HER2-positive, hormone-receptor negative, early stage or locally advanced breast cancer. The tolerability, safety and immunogenicity profiles of the two agents were also similar. No new safety or immunogenicity concerns were observed following a switch from neoadjuvant reference pertuzumab to adjuvant HLX11. The role of reference pertuzumab in the management of HER2-positive breast cancer is well established, and HLX11 provides an effective biosimilar alternative for patients requiring pertuzumab therapy.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilars: A Virtuous Cycle of Sustainability and Innovation.","authors":"Fernando de Mora, Vicente Merino-Bohórquez, Rosario García-Vicuña, Isabel Río-Álvarez","doi":"10.1007/s40259-026-00806-9","DOIUrl":"https://doi.org/10.1007/s40259-026-00806-9","url":null,"abstract":"<p><p>A biosimilar is a biological medicinal product developed to replicate a licensed originator-i.e., the reference product-with which it shares quality, efficacy, and safety. Marketed following expiry of the reference product's patent protection, biosimilars introduce competition that benefits patients and foster sustainability. In addition to such sustainability of healthcare systems, biosimilars confer a less widely recognized yet equally important benefit: they stimulate innovation. The European regulatory framework, pioneered by the European Medicines Agency and reinforced by other reference regulatory bodies, has unlocked this innovative potential. This paper examines how the development, manufacturing, commercialization, and clinical use of biosimilars generate advances in healthcare delivery. Drawing on available evidence and market experience, it proposes a classification of biosimilar-driven innovation into three domains: pharmaceutical innovation, technological innovation, and therapeutic innovation. Benefits wholly or partially attributable to biosimilars encompass both incremental and disruptive improvements within each domain. These include, for instance, the reinvestment of resources into novel therapies and technologies; therapeutic paradigm shifts supported by evidence and increasingly reflected in clinical guidelines; and enhanced formulations and delivery devices. Although relevant to all healthcare stakeholders, this paper is primarily directed at physicians. As key facilitators of biosimilar adoption, they will find that the innovative aspects of these medicines offer both compelling arguments to support broader prescribing and practical examples of how biosimilars can enhance clinical practice and improve patient outcomes.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologic Therapies for Alleviating Neurodegeneration in Lysosomal Storage Diseases.","authors":"Liyan Qiu, Jonas Torbjörn Ungerbäck, Eric Paul Bennett, Rasmus O Bak","doi":"10.1007/s40259-026-00804-x","DOIUrl":"https://doi.org/10.1007/s40259-026-00804-x","url":null,"abstract":"<p><p>Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders characterized by lysosomal dysfunction and progressive accumulation of undegraded substrates, leading to multisystem involvement and, in many cases, severe neurodegeneration. Because the blood-brain barrier (BBB) restricts central nervous system (CNS) access for most therapeutic modalities, neurological manifestations remain the major unmet need across LSDs. In this review, we summarize current and emerging strategies aimed at correcting CNS pathology, including enzyme replacement therapy (ERT), adeno-associated virus (AAV)-mediated gene therapy, allogeneic hematopoietic stem cell transplantation (HSCT), and autologous HSCT with gene-modified hematopoietic stem cells. While ERT provides limited CNS benefits and allogeneic HSCT mitigates neurodegeneration only partially, their overall impact on CNS outcomes remains restricted. Newer approaches, such as BBB-shuttling ERTs, CNS-tropic AAV capsids, and genetically modified autologous hematopoietic stem and progenitor cells capable of sustained supraphysiological enzyme production, offer promising avenues for enhanced CNS delivery and cross-correction. Together, these advances underscore a shift toward integrated therapeutic strategies that combine systemic and CNS-directed interventions, with the potential to transform outcomes for patients with LSDs and other neurodegenerative disorders amenable to cross-correction.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.","authors":"Ted R Mikuls, Tuhina Neogi, Angelo Gaffo","doi":"10.1007/s40259-026-00808-7","DOIUrl":"https://doi.org/10.1007/s40259-026-00808-7","url":null,"abstract":"<p><p>Disease-modifying antirheumatic drugs (DMARDs) are immune-modifying agents that have shown efficacy in improving response rates and reducing infusion reactions associated with uricase therapy for uncontrolled gout by inhibiting anti-drug antibody (ADA) formation. However, increased gout flare rates following initiation of uricase therapy remain a concern, impacting patient quality of life and treatment adherence. Gout flares are an acute inflammatory reaction to monosodium urate crystals, driven by inflammasome activation. As such, it is possible that DMARDs could impact gout flare risk. In this hypothesis-generating narrative review, we have synthesized mechanistic data investigating the effects of the DMARDs methotrexate, mycophenolate mofetil, azathioprine, leflunomide, and sirolimus on mechanisms involved in gout flare such as NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation. The mechanisms by which DMARDs inhibit ADA formation appear to be distinct from those that may affect gout flares, but these may exist in balance with one another to form a distinct pharmacological profile for each agent. Paradoxically, preclinical evidence suggests that DMARDs may sometimes induce NLRP3 inflammasome activation, particularly at higher doses. We suggest that individual DMARDs' effect on inflammatory pathways relevant to gout flare may vary depending on the pathophysiological context and differences in their pharmacological profiles. Therefore, the inflammatory consequences of combining DMARDs with uricase therapy are likely to be specific to the individual agent. Understanding the mechanistic profile of each DMARD is key to optimizing both immunogenicity management and flare outcomes in patients receiving uricase therapy for uncontrolled gout.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Anti-drug Antibodies on the Bioavailability of Alglucosidase Alfa in Classic Infantile Pompe Disease.","authors":"Martha Caterina Faraguna, Daniël A M Lambregts, Ina Barzel, Edwin H Jacobs, Marianne Hoogeveen-Westerveld, Nadine A M E van der Beek, W W M Pim Pijnappel, Serena Gasperini, Tim Preijers, Johanna M P van den Hout, Ans T van der Ploeg","doi":"10.1007/s40259-026-00802-z","DOIUrl":"https://doi.org/10.1007/s40259-026-00802-z","url":null,"abstract":"<p><strong>Background: </strong>The impact of anti‑drug antibodies (ADAs) on the bioavailability of recombinant human acid α-glucosidase (rhGAA) in classic infantile Pompe disease remains incompletely understood.</p><p><strong>Objective: </strong>The aim of this study was to investigate the effects of ADAs on the bioavailability of rhGAA in classic infantile Pompe disease.</p><p><strong>Methods: </strong>We analyzed 15 pharmacokinetic (PK) curves from 13 patients receiving rhGAA. High titers were defined as ≥ 1:31250. Alpha-glucosidase activity in plasma was measured using protein A beads to precipitate ADA-bound rhGAA, and sepharose as control. Neutralizing effects were assessed in fibroblasts and culture medium after incubation with patient sera and a fixed amount of rhGAA. Peak activity (C_max) and area under the curve (AUC) were calculated by non-compartmental analysis.</p><p><strong>Results: </strong>rhGAA bioavailability was affected in six of nine high-titer patients (n = 1, 1:31,250; n = 5, ≥ 1:156,250). AUC was reduced by 11-52% in the protein A assay compared with sepharose (n = 5). Fibroblast uptake studies demonstrated neutralizing effects with intracellular enzyme activity reduced to 47-71% (n = 5). No ADA effect was detectable in three patients. At the group level, high-ADA patients showed significantly lower C_max in both assays and a lower AUC in the protein A assay compared with non-high-ADA patients. Slower infusion schemes, as management for infusion-associated reactions, correlated inversely with C_max (R = - 0.64), but not AUC. Immunomodulation eliminated the effects of ADAs, as shown in two patients.</p><p><strong>Conclusions: </strong>High ADAs have heterogenous effects on rhGAA bioavailability. Titers ≥1:156,250, mostly, had a measurable effect, capturing up to > 50% of infused rhGAA. A high titer, per se, did not imply neutralizing effects. Where available, functional assays, including PK curves and uptake studies, may contribute to characterize ADA effects.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ustekinumab Biosimilars versus Reference Ustekinumab for Moderate-to-Severe Plaque Psoriasis: A Pre-switch Systematic Review and Meta-analysis.","authors":"Carlos Roberto Montes-de-Oca-Saucedo, Laura Ghanem, Najwaa Kirmani, Bruno Briceño-Villardaga, Andrea Michelle Talancon-Solana, Adela Jatzari Salinas-Ocampo, Grecia Sereno-Acevedo, Adolfo Soto-Domínguez, Raquel Rivera-Díaz","doi":"10.1007/s40259-026-00795-9","DOIUrl":"10.1007/s40259-026-00795-9","url":null,"abstract":"<p><strong>Background: </strong>Ustekinumab biosimilars have expanded treatment options for moderate-to-severe plaque psoriasis, but pooled evidence is needed to determine whether they achieve therapeutic equivalence to reference ustekinumab during the initial randomized comparative period before protocol-defined switching.</p><p><strong>Objectives: </strong>The aim of this systematic review was to assess the therapeutic equivalence of ustekinumab biosimilars versus reference ustekinumab during the pre-switch period in adults with moderate-to-severe plaque psoriasis.</p><p><strong>Methods: </strong>We searched PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and trial registries from inception to 15 October 2025 for phase III randomized clinical trials comparing ustekinumab biosimilars or follow-on biologics with reference ustekinumab and reporting comparative data before switching. Data were extracted independently by two reviewers. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman 95% confidence intervals (CIs) was performed. The primary outcome was 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at week 12, analyzed using risk differences with a prespecified equivalence margin of ± 10%.</p><p><strong>Results: </strong>Nine randomized trials including 4532 participants were analyzed. At week 12, the pooled risk difference for PASI 75 was 0.02 (95% CI -0.02 to 0.05), meeting the prespecified ± 10% equivalence criterion, with low between-study heterogeneity (I² statistic = 6%). Equivalence-consistent estimates were also observed for PASI 90 (risk difference - 0.01, 95% CI - 0.06 to 0.03) and PASI 100 (risk difference 0.00, 95% CI - 0.03 to 0.03). Treatment-emergent adverse events were comparable through week 28 (risk difference 0.01, 95% CI - 0.04 to 0.06). At week 12, anti-drug antibody detection was lower in biosimilar arms (risk difference - 0.14, 95% CI - 0.23 to - 0.04), which may partly reflect assay variability rather than clinically meaningful differences. No material differences were observed in short-term pre-switch clinical response, patient-reported quality of life, or safety.</p><p><strong>Conclusions: </strong>During the initial randomized comparative period, ustekinumab biosimilars met prespecified therapeutic equivalence criteria for PASI 75 and showed equivalence-consistent results for PASI 90 and PASI 100, with comparable short-term safety versus reference ustekinumab. These findings provide pooled reassurance across standard and stringent skin-clearance outcomes during a clinically relevant early treatment window.</p><p><strong>Registration: </strong>PROSPERO (CRD420251166323). Registered October 12, 2025.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"869-882"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.","authors":"Rebecca J Wilson, Charmaine A Ramlogan-Steel, William J Deasy, Sarah J Greenstein, Christopher J Layton, Jason C Steel","doi":"10.1007/s40259-026-00794-w","DOIUrl":"10.1007/s40259-026-00794-w","url":null,"abstract":"<p><p>Uveal melanoma is the most common primary intraocular malignancy in adults and remains associated with poor outcomes once metastatic disease develops. Despite advances in local tumour control and molecular prognostication, effective systemic therapies capable of delivering durable benefit are limited. A range of gene-based therapeutic strategies have been explored in uveal melanoma, including immune-based approaches, gene-modified cell therapies and direct gene delivery. While these strategies have yielded important biological insights and modest clinical advances, their broader impact has been constrained by challenges related to delivery, tumour specificity, durability of effect and translational feasibility. This review surveys the current landscape of gene-based therapies investigated in uveal melanoma and synthesises lessons learned from these approaches, with a particular emphasis on the delivery platform as a determinant of therapeutic success. We examine the emerging potential of adeno-associated virus vectors as gene-delivery platforms for uveal melanoma, drawing on their safety profile and capacity for sustained transgene expression. We highlight the need for adaptation beyond native adeno-associated virus serotypes and discuss advances in capsid engineering, targeting strategies and control mechanisms that enable tumour-selective gene delivery. Finally, we consider translational challenges and future directions for integrating targeted adeno-associated virus-based approaches into therapeutic strategies for uveal melanoma.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"801-819"},"PeriodicalIF":8.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}