BioDrugs最新文献

{"title":"Site-Specific Genomic Markers Associated with Outcomes of PD-1 Blockade in Gastric and Esophagogastric Junction Cancer: Analysis of Japan's C-CAT Registry.","authors":"Yasuyoshi Sato, Koichi Yagi, Kazunaga Ishigaki, Raito Asaoka, Kotaro Sugawara, Shuichiro Oya, Asami Okamoto, Yoshiyuki Miwa, Shoh Yajima, Yoshifumi Baba, Kousuke Watanabe, Katsutoshi Oda, Mitsuhiro Fujishiro","doi":"10.1007/s40259-026-00779-9","DOIUrl":"10.1007/s40259-026-00779-9","url":null,"abstract":"<p><strong>Background: </strong>Only a minority of patients with advanced gastric cancer (GC) or esophagogastric junction (EGJ) adenocarcinoma derive durable benefit from anti-programmed cell death 1 (PD-1) therapy. However, reliable biomarkers for real-world clinical decision-making remain limited.</p><p><strong>Objective: </strong>To identify tumor site-specific genomic alterations associated with outcomes of nivolumab monotherapy in a nationwide real-world cohort.</p><p><strong>Methods: </strong>We conducted a retrospective nationwide analysis using Japan's Center for Cancer Genomics and Advanced Therapeutics (C-CAT) registry, including patients with GC and EGJ cancer adenocarcinoma treated with nivolumab monotherapy (July 2019-April 2024). Primary endpoints were time to treatment failure (TTF) and overall survival (OS), defined as the interval from nivolumab initiation to death from any cause; objective response rate (ORR) was secondary. Gene-level alteration indicators were derived from vendor-reported tumor-only panel calls across multiple platforms and filtered for clonal hematopoiesis of indeterminate potential (CHIP)-like variants (variant allele frequency < 0.05). Multivariable models adjusted for age and sex were fitted separately for GC and EGJ cancer. Variant pathogenicity was based on available panel annotations; therefore, gene-level results should be interpreted as exploratory findings.</p><p><strong>Results: </strong>Among 798 patients with GC and 114 patients with EGJ cancer adenocarcinoma, median TTF/OS/ORR were 3.98 months/20.2 months/11.7% in GC and 4.80 months/24.7 months/14.9% in EGJ cancer adenocarcinoma. In GC, ASXL1 mutation remained independently associated with longer TTF (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.37-0.94) after adjustment and CHIP filtering. For OS, microsatellite instability-high [MSI-H] (HR 0.16, 95% CI 0.04-0.70) and FANCG (HR 0.37, 95% CI 0.16-0.87) were associated with longer OS, whereas CDH1 (HR 1.51, 95% CI 1.10-2.05) was associated with shorter OS. In EGJ cancer adenocarcinoma, NTRK1 mutation correlated with longer TTF (HR 0.31, 95% CI 0.10-0.98) and MUTYH with shorter OS (HR 5.68, 95% CI 2.04-15.81), both exploratory.</p><p><strong>Conclusions: </strong>In this large Japanese real-world cohort, genomic associations with nivolumab outcomes differed by tumor site. In gastric cancer, ASXL1 mutation was associated with prolonged treatment benefit under PD-1 blockade, while CDH1 and FANCG showed exploratory associations with OS. These findings warrant further validation in prospective and platform-controlled analyses.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"497-516"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761351","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":"Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.","authors":"Umar Iqbal, Roy W Hwang, Will J Costain","doi":"10.1007/s40259-026-00782-0","DOIUrl":"10.1007/s40259-026-00782-0","url":null,"abstract":"<p><p>Peripherally administered therapeutics for neurological indications are challenged with anatomical and physiological barriers that limit their ability to access their site of action in the central nervous system (CNS). This is particularly true for complex therapeutics such as antibodies, immunotherapeutics, and gene therapies. The blood-brain barrier is the specialized structure that functionally regulates the ability of blood constituents to access the CNS. Blood-brain barrier delivery technologies for protein therapeutics have been established in pre-clinical models and are beginning to be verified in clinical studies. Technologies reliant on the transcellular pathway across the blood-brain barrier utilize the receptor-mediated transcytosis mechanism. Research into the use of lipid nanoparticles (LNPs) to deliver complex therapeutics has tremendously expanded in recent years. Lipid nanoparticles represent a compelling alternative to viral vectors for the delivery of various gene therapy modalities, including messenger RNA, small interfering RNA, and antisense oligonucleotides. Functionalization of LNPs with blood-brain barrier-penetrant moieties is being explored as a means to enable CNS delivery of LNP-based therapeutics. The recent innovations and validation of LNP-based delivery systems have hastened the fulfillment of the promise of facile CNS-targeted gene therapies. This review focuses on functional aspects of the blood-brain barrier and how they relate to recent advances in LNP technologies for CNS delivery, as well as their potential impact on gene therapy.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"407-431"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761253","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":"The Market for Monoclonal Antibodies: Trends, Challenges, and Opportunities.","authors":"André Soares Motta-Santos, Kenya Valéria Micaela de Souza Noronha, Leonardo Costa Ribeiro, Jeffrey Gow, Khorshed Alam, Mônica Viegas Andrade","doi":"10.1007/s40259-026-00774-0","DOIUrl":"10.1007/s40259-026-00774-0","url":null,"abstract":"<p><strong>Objective: </strong>This study examines the monoclonal antibody innovation landscape through patent activity and market data.</p><p><strong>Methods: </strong>A dedicated dataset was constructed by linking multiple sources (Antibody Society, Orange Book, Ark Patent Intelligence, US Patent and Trademark Office, PATSTAT, Purple Book, US Veterans Affairs, US-FDA, and ORBIS), covering patents registered between 1986 and 2019. Data analysis comprised six components: (i) a general description of the dataset, (ii) an examination of monoclonal antibody patents and approval trends, (iii) an analysis of therapeutic indications, (iv) a characterization of patent holders and producers through descriptive and network analyses, (v) an assessment of shareholder influence, including common-ownership patterns, and (vi) an evaluation of monoclonal antibody prices.</p><p><strong>Results: </strong>The dataset included 63 monoclonal antibodies, 1732 unique patents, 89 active pharmaceutical ingredients, 34 producers, and 214 therapeutic indications, of which 36.5% were single indication, while the average number of secondary indications was 3.78. Roche, Johnson & Johnson, Eli Lilly, Amgen, and Novartis led reference medicine production, while Amgen and Pfizer were notable in biosimilars, with only five companies producing both. Shareholders such as BlackRock, UBS, Vanguard, and JPMorgan exerted strong market influence in monoclonal antibody production. Prices were extremely high, averaging US$127,430 per course or year (s = US$142,509), with 42.1% of monoclonal antibodies priced above US$100,000.</p><p><strong>Conclusions: </strong>While monoclonal antibodies have transformed modern medicine and improved safety and effectiveness, their persistently high prices, reinforced by market concentration and financial investor influence, raise serious concerns for equity and social welfare.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"517-537"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572429","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":"Effectiveness of Lebrikizumab Treatment for Patients with Atopic Dermatitis Switched from Dupilumab or Tralokinumab: A 48-Week Real-World Retrospective Study.","authors":"Teppei Hagino, Hidehisa Saeki, Eita Fujimoto, Naoko Kanda","doi":"10.1007/s40259-026-00772-2","DOIUrl":"10.1007/s40259-026-00772-2","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"493-495"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430624","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":"Advanced Combination Therapy in Inflammatory Bowel Disease: What Does the Future Hold?","authors":"Piotr Eder, Adam Fabisiak, Hubert Zatorski, Liliana Łykowska-Szuber, Kamila Stawczyk-Eder, Katarzyna Waszak, Magdalena Gawron-Kiszka, Patrycja Dudek, Katarzyna Bzdęga, Renata Talar-Wojnarowska","doi":"10.1007/s40259-026-00770-4","DOIUrl":"10.1007/s40259-026-00770-4","url":null,"abstract":"<p><p>In recent years, substantial progress has been achieved in the development of novel therapeutic options for inflammatory bowel disease (IBD). Despite these advances, a significant proportion of patients continue to experience either primary nonresponse or secondary loss of response to biologic agents or small-molecule therapies. In addition, many patients present with heterogeneous and often difficult-to-manage extraintestinal manifestations, highlighting the persistent unmet needs in IBD management. Consequently, multiple therapeutic strategies have been explored to overcome these challenges and to improve long-term disease control. Among emerging approaches, advanced combination therapy (ACT)-defined as the concomitant use of monoclonal antibodies and/or oral small-molecule agents with distinct mechanisms of action-has attracted increasing interest in recent years. ACT aims to enhance therapeutic efficacy, address complex disease phenotypes, and potentially prevent or delay treatment failure. In this review, we summarize the currently available evidence on how to optimally apply combination therapeutic strategies in IBD. Key aspects discussed include the rationale for selecting agents with complementary mechanisms of action, the hypothetical timing and duration of combination treatment, and the clinical criteria that may guide the selection of specific ACT algorithms. Evidence derived from real-world studies and completed randomized clinical trials, including the landmark VEGA trial, is critically reviewed. Furthermore, we present data from ongoing clinical trials-both industry- and investigator-initiated-as well as emerging research on bispecific therapeutic molecules in IBD, which combine two molecular targets within a single compound. Together, these data provide a comprehensive overview of the current and future role of ACT in IBD management.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"361-380"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372210","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":"Programmed Cell Death Protein 1-Interleukin-2 Bispecific Agents for Cancer Therapy.","authors":"Chang Xu, Tingxu Yan, Shuo Wen, Can Wu, Tingmin Chang, Eryan Kong, Huicong Liu","doi":"10.1007/s40259-026-00769-x","DOIUrl":"10.1007/s40259-026-00769-x","url":null,"abstract":"<p><p>Programmed Cell Death Protein 1 (PD-1) / Programmed Cell Death Ligand 1 (PD-L1) inhibitors have revolutionized cancer immunotherapy but are limited by low response rates and drug resistance. Interleukin-2 (IL-2), a potent T-cell activator, is clinically restricted due to regulatory T cell (Treg) activation and severe systemic toxicity. PD1-IL2 bispecific drugs, integrating PD-1 blockade and engineered IL-2 variants (IL-2v) into a single molecule, precisely regulate tumor microenvironment immunity to overcome these limitations. This review summarizes their latest progress, including the synergistic mechanism of PD-1/PD-L1 and IL-2 signaling, molecular designs (e.g., βγ-biased IL-2v and Innovent's α-biased IBI363), and 'cis delivery' for targeted activation. Preclinical and clinical data (e.g., IBI363) show encouraging anti-tumor activity and improved safety in advanced tumors, benefiting PD-1-resistant patients. Challenges remain, such as unclear mechanisms, drug resistance, and long-term safety. Future advancements rely on optimized molecular design, combination therapies, and predictive biomarkers, driving PD1-IL2 bispecific drugs toward more precise and effective tumor immunotherapy for broader patient populations.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"459-478"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670363","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":"Correction: Real-World Use of Dostarlimab Plus Chemotherapy in Advanced or Recurrent Endometrial Cancer: A Nationwide Cohort Study in France.","authors":"Allison Singier, Stéphane Vignot, David Desplas, Mahmoud Zureik, Nadia Haddy","doi":"10.1007/s40259-026-00778-w","DOIUrl":"10.1007/s40259-026-00778-w","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"565"},"PeriodicalIF":6.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833152","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":"Progress in Designing Cytokine Antagonist Antibodies for Cancer Therapy.","authors":"Henry McEacheron, Giulia Nisita, Peiying Liu, Jamie B Spangler","doi":"10.1007/s40259-026-00777-x","DOIUrl":"10.1007/s40259-026-00777-x","url":null,"abstract":"<p><p>Cytokines are a class of secreted proteins that transmit critical signals between cells to maintain homeostatic balance, coordinating processes such as proliferation, migration, polarization, and survival. Cytokines play a particularly important role in regulating the immune system through activation of either proinflammatory or anti-inflammatory pathways on a variety of hematopoietic and nonhematopoietic cell types. As a consequence of their essential roles in dictating cell fate, especially in the context of immune responses, cytokines have become an appealing target for the development of drugs to treat immune-linked diseases. With respect to oncology applications, therapeutic efforts have primarily focused on either promoting the effects of immunostimulatory cytokines or antagonizing the effects of immunosuppressive cytokines, with the goal of stimulating antitumor immunity. Here, we provide an updated overview of preclinical and clinical therapeutic advances in the design of cytokine antagonist antibodies for cancer treatment. We first discuss the structural and functional characteristics of various cytokines, including interleukins, chemokines, and growth factors, as well as their contributions to cancer development and progression. We then highlight successes and failures in generating therapeutic antibodies against each of these cytokines. As the functions of cytokines are complex and multifaceted, we note that complete ablation of cytokine activity may not be therapeutically desirable and that combination strategies are often needed to realize the full potential of anti-cytokine antibodies as therapies. Looking ahead, innovative approaches and novel antagonistic scaffolds promise to continue advancing clinical progress for this important category of oncology drugs.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"381-406"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670361","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":"Interleukin-23 Inhibitors in Inflammatory Bowel Disease.","authors":"Pierluigi Puca, Simone Parello, Stefania Colantuono, Antonio Tursi, Gaetano Coppola, Loris Riccardo Lopetuso, Franco Scaldaferri, Antonio Gasbarrini, Alfredo Papa","doi":"10.1007/s40259-026-00781-1","DOIUrl":"10.1007/s40259-026-00781-1","url":null,"abstract":"<p><p>Selective inhibition of interleukin-23 (IL-23) has emerged as a highly effective therapeutic strategy in inflammatory bowel disease, targeting a central pathway of chronic intestinal inflammation while preserving host defense mechanisms. Across phase II and phase III randomized controlled trials, risankizumab, mirikizumab, and guselkumab consistently demonstrated robust efficacy in both ulcerative colitis and Crohn's disease, achieving clinical remission rates approaching 40-50% in ulcerative colitis and exceeding 50% in Crohn's disease during maintenance, with parallel improvements in endoscopic and histological outcomes. Notably, mirikizumab and guselkumab showed particularly high rates of endoscopic and histological remission in ulcerative colitis, whereas guselkumab achieved some of the highest induction remission rates in Crohn's disease. These benefits were durable over time, with long-term extension studies confirming sustained remission beyond two years in a substantial proportion of patients. Across trials, IL-23 inhibitors displayed a favorable safety profile, with low rates of serious adverse events, infections, and major cardiovascular events, supporting their use in long-term disease management. Real-world evidence further reinforces these findings, demonstrating consistent effectiveness in heavily pretreated and complex patient populations, including those with prior biologic failure, comorbidities, or difficult-to-treat disease phenotypes. In particular, risankizumab has shown strong performance in multi-refractory Crohn's disease cohorts, while emerging data for mirikizumab confirm its effectiveness in real-life ulcerative colitis settings. Beyond clinical outcomes, differences in molecular structure, pharmacokinetics, and Fc-mediated interactions may contribute to subtle distinctions among agents, potentially influencing therapeutic positioning. Ongoing development of oral compounds and combination strategies targeting complementary inflammatory pathways is expected to further expand the role of IL-23 inhibition. Overall, interleukin-23 inhibitors represent a cornerstone of modern inflammatory bowel disease therapy, combining high efficacy, durable responses, and an excellent safety profile, with growing evidence supporting their use across a broad spectrum of patients.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"479-492"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761345","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":"In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.","authors":"Xiaoyi Dong, Wei Yan, Xinmiao Long, Minghua Wu","doi":"10.1007/s40259-026-00771-3","DOIUrl":"10.1007/s40259-026-00771-3","url":null,"abstract":"<p><p>Adoptive cell therapies involving chimeric antigen receptor (CAR)-T cells have been demonstrated to be efficient treatments for hematologic malignancies and have successfully completed clinical translation. While traditional ex vivo T-cell engineering is still limited by challenges such as time-consuming processes, high costs, and poor controllability, as an emerging strategy, in vivo T-cell engineering involves the generation of functional effector T cells directly within patients through several injections of delivery vectors, which can reach cell therapies in days, further reducing costs and increasing scalability. This review logically outlines the technical development and application of in vivo T-cell engineering, with a particular focus on innovations in delivery systems, in which we elaborate on the mechanism and latest advances in viral vector platforms and RNA-based platforms. Furthermore, we analyzed the delivery platforms of multiple therapeutic candidates and their available data, discussing their therapeutic efficacy and safety profiles in both animal models and clinical applications. Although some challenges remain in solid tumor targeting, precise regulation, and manufacturing, increasing preclinical and clinical data have revealed the immense therapeutic potential of in vivo programming strategies across a broad spectrum of diseases.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"433-458"},"PeriodicalIF":8.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442533","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}