mAbs最新文献

{"title":"Subcutaneous drug delivery of high concentration antibody products - part 2: formulation, device options, and clinical bridging strategies for patient-centric commercial presentations.","authors":"Indrajit Ghosh, Suyash Deodhar, Hiten Gutka, Srini Sridharan, Dilbir Bindra","doi":"10.1080/19420862.2026.2680773","DOIUrl":"10.1080/19420862.2026.2680773","url":null,"abstract":"<p><p>The landscape of drug delivery is undergoing a transformative shift. As demand for large-volume subcutaneous (SC) biologics continues to surge, the race to develop smarter, patient-centered combination drug products has never been more urgent. Here, we present a comprehensive analysis of SC combination drug product development from a commercial landscape perspective, with a focus on the dynamic interaction between delivery devices, biopharmaceutical formulation attributes, and clinical bridging strategies. From pre-filled syringes and auto-injectors to next-generation infusion pumps and on-body delivery systems, this review maps the full spectrum of delivery platforms, highlighting key factors from patient usability and tolerability to therapeutic performance and real-world preferences that drive trade-offs <b>in</b> the selection of one format over another. Furthermore, formulation strategies to support high-dose SC delivery via increased concentration, volume, or both are explored. Crucially, this review bridges the gap between bench and bedside, demonstrating clinical bridging strategies with multiple case studies that are essential for translating device-formulation decisions into outcomes that are both clinically meaningful and patient-friendly.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2680773"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13248910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199490","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":"Artificial intelligence-assisted design of MAGE-A4 ×CD16 T-cell receptor-like natural killer cell engagers.","authors":"Yang Liu, Hongsen Peng, Xing Fan, Xiaoxi Liu, Guanda Jiao, Jialin Li, Tiantian Wang, Simon James Fong, Lipeng Zhu, Yeneng Dai, Qi Zhao","doi":"10.1080/19420862.2026.2717991","DOIUrl":"10.1080/19420862.2026.2717991","url":null,"abstract":"<p><p>The cancer-testis antigen MAGE-A4 is an attractive immunotherapy target due to its high expression in various malignancies and restricted expression in normal tissues. Peptides derived from intracellular MAGE-A4 are presented on the cell surface by HLA-A*02:01, enabling targeting by T-cell receptor (TCR)-like molecules. We identified a TCR-like antibody recognizing the HLA-A *02:01-presented MAGE-A4 GVY230-239 peptide complex through yeast-display screening, computational structural prioritization, and experimental validation. Diverging from T-cell engagers, we engineered this binder into a natural killer cell engager (NKCE) by fusing it with a CD16-targeting variable domain of heavy-chain-only antibody (VHH) in an IgG format. This MAGE-A4-directed NKCE demonstrated potent and specific cytotoxicity against MAGE-A4⁺/HLA-A*02:01⁺ tumor cell lines. To distinguish conventional Fc-mediated signaling from VHH-mediated CD16a engagement, we introduced the Fc-silencing N297A mutation. The mutation markedly reduced reporter activation by the parental IgG format, whereas the VHH-containing NKCE retained CD16a reporter activity. Reporter activation was measurable in the absence of target cells and increased further following addition of A375 cells. In cytotoxicity assays, the NKCE mediated target- and CD16a-dependent killing in the tested in vitro models. These findings provide in vitro proof of concept for a MAGE-A4-directed NKCE and support further preclinical evaluation, including cytokine profiling, safety assessment, and in vivo efficacy studies.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2717991"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865594","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":"Multi-modal feature learning to prioritize ADCs with favorable half-life in mice.","authors":"Xiang-Wei Zhu, Khushboo Jani, Wenjia Gu, Mia Guterman, Valery R Polyakov, Hans-Peter Gerber, Werner Rubas","doi":"10.1080/19420862.2026.2657646","DOIUrl":"10.1080/19420862.2026.2657646","url":null,"abstract":"<p><p>Favorable pharmacokinetic (PK) properties of antibody-drug conjugates (ADCs) enable higher systemic exposure and are associated with improved clinical efficacy, yet ADC PK optimization remains largely empirical and resource-intensive. We developed an <i>in silico</i> framework to predict half-lives of monoclonal antibodies (mAbs) and ADCs in C57BL/6 mice using multi-modal feature learning. To address structural complexity of ADCs, each compound was deconvoluted into three components: (1) antibody features represented using sequence descriptors, AlphaFold-based structural properties, or protein language model (PLM) embeddings; (2) conjugation-related features, including drug-to-antibody ratio and conjugation sites; and (3) physicochemical properties of linker-payloads. XGBoost models were trained using experimental half-life data from 118 mAbs and ADCs. Structure-based and PLM approaches achieved strong cross-validation (Pearson's <i>r</i> = 0.76), outperforming sequence-only models. In temporal validation of 32 mAbs and ADCs, the structure-based models demonstrated robust generalization (<i>r</i> = 0.79). PLM embeddings achieved comparable rank ordering (Spearman's <i>ρ</i> up to 0.81 for ESM-2), but lower quantitative accuracy relative to structure-based models. Overall, our study presents a scalable machine learning framework for early PK screening of mAbs and ADCs prior to synthesis and <i>in vivo</i> testing.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2657646"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717194","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":"Safety, tolerability, and pharmacokinetics/-dynamics of the dipeptidyl peptidase 3-inhibiting antibody Procizumab in a first-in-human trial.","authors":"Dirk van Lier, Louis Mourisse, Hákon Hollander, Karine Santos, Andreas Bergmann, Antonius Eduard van Herwaarden, Matthijs Kox, Peter Pickkers","doi":"10.1080/19420862.2026.2671468","DOIUrl":"10.1080/19420862.2026.2671468","url":null,"abstract":"<p><p>Dipeptidyl peptidase 3 (DPP3), an aminopeptidase that degrades several key cardiovascular mediators, may induce and exacerbate hemodynamic instability during cardiogenic shock. Procizumab (PCZ) is a first-in-class humanized monoclonal antibody that inhibits DPP3 activity. In preclinical shock models, PCZ increased angiotensin metabolite levels, improved cardiovascular function, and increased survival. Here, results are presented for a first-in-human Phase 1 trial (NCT06331884) that evaluated the safety, tolerability, and pharmacokinetics and pharmacodynamics of PCZ. Twenty-four healthy male volunteers were enrolled in a randomized, double-blind, placebo-controlled Phase 1 trial. Participants (<i>n</i> = 6 per group) received placebo or one of three doses of PCZ (3 mg/kg, 6 mg/kg, and 12 mg/kg). Participants were monitored clinically for 24 h after drug administration, as well as at 6 follow-up visits performed during a 28-d period. Adverse events associated with PCZ were predominantly mild, and no serious adverse events were reported. Local tolerability, vital signs, laboratory assessments, and electrocardiograms did not reveal any safety concerns. PCZ exhibited a terminal elimination half-life of 24, 34, and 53 h in the low, intermediate, and high-dose groups, respectively. A volume of distribution of roughly 9.8-10.2 liters indicates that the drug predominantly remains within the circulation. Results of this trial are currently being followed up in the PROCARD Phase 1b/2a (NCT06832722) study, which is evaluating safety and determining the optimal dose of PCZ in cardiogenic shock patients.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2671468"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982260","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":"Generation of human sequence antibodies in OmniChicken against the highly conserved mammalian target BDNF using three distinct discovery workflows.","authors":"Kathryn H Ching, Sinéad Keating, Baisen Zeng, Diego A Espinosa, Edwina Stack, Siobhan Wall, Sonia Beyer, Jason Wade, Amy Tam, Orla Cunningham, Robayet Chowdhury, Yulei Zhang, Jacqueline Morales, Yasmina Abdiche, Philip A Leighton, Alfredo Darmanin Sheehan, William Harriman","doi":"10.1080/19420862.2026.2672771","DOIUrl":"10.1080/19420862.2026.2672771","url":null,"abstract":"<p><p>Generation of antibodies against highly conserved mammalian targets remains a substantial challenge in the therapeutic antibody space. Naïve and synthetic libraries address this need through rounds of <i>in vitro</i> affinity maturation. <i>In vivo</i> affinity matured antibodies from hyperimmunization often fail to generate diverse repertoires against conserved targets. Phylogenetically distant species offer an alternative strategy to obtain <i>in vivo</i> affinity-matured antibodies against conserved targets. We used OmniChicken, a transgenic chicken that expresses fully human heavy and light immunoglobulin genes, to generate antibodies against brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that is dysregulated in chronic pain syndromes and neurological diseases such as Alzheimer's disease. Mature BDNF is 100% conserved between humans and mice. Following immunization of a cohort of OmniChickens, splenocytes were screened using three discovery workflows: Gel Encapsulated Microenvironment (GEM) and xPloration®, which are both single B cell screening platforms, and phage display. In total, we isolated 110 unique antibodies representing 29 unique VH and 32 unique VL lineages, many of which overlapped across the three platforms. Assessment of immunogenicity, including T cell epitope content and \"humanness\" showed that the cohort compared favorably with a clinical reference set, while biophysical analysis was consistent with good developability characteristics. EC50s were comparable to a benchmark clone, R3bH01, previously developed from a wild-type chicken. Finally, an ELISA-based IC50 assay identified clones from each platform with neutralizing activity. Overall, all three discovery workflows identified diverse lineages of antibodies with desirable developability properties and functionally relevant binding characteristics.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2672771"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157041","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":"Optimization strategies for monoclonal antibody production: advances in simulation and artificial intelligence in bioprocessing.","authors":"Kadeejathul Kubra, Munawar A Shaik","doi":"10.1080/19420862.2026.2706886","DOIUrl":"10.1080/19420862.2026.2706886","url":null,"abstract":"<p><p>The rapid growth of monoclonal antibody (mAb) therapies has increased the need for efficient, scalable, and affordable manufacturing processes. However, mAb production remains complex because of nonlinear upstream cell culture behavior, expensive downstream purification, especially Protein-A chromatography, and plant-level bottlenecks that can increase cost, cycle time, and manuacturing uncertainty. This review examines recent developments in mAb manufacturing with focus on process simulation, mathematical optimization, and artificial intelligence/machine learning (AI/ML) across upstream processing (USP), downstream processing (DSP), and integrated plant-level operation. In USP, media optimization, dynamic feeding, high-density cultures, and continuous perfusion bioreactors are discussed in relation to productivity and critical quality attributes (CQAs). In DSP, alternative and intensified purification strategies are reviewed with a focus on recovery, impurity clearance, scalability, cost, and technology maturity. AI/ML applications are also discussed from early-stage development and cell-line screening to upstream control, CQA prediction, chromatography optimization, and downstream decision support. Despite these advancements, challenges such as data heterogeneity, limited standardized datasets, model transferability, and regulatory constraints remain important barriers to implementation. Overall, this review uniquely connects simulation and AI/ML approaches to practical optimization across the full mAb manufacturing workflow, including design, scheduling, debottlenecking, purification, monitoring, and quality prediction. The combination of process simulation, continuous bioprocessing, and AI/ML-based decision support may enable more flexible, reliable, and cost-effective mAb manufacturing. However, these benefits depend on validation through robust models, process-specific case studies, and technoeconomic analysis.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2706886"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579156","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":"Bispecific antibodies that engage pIgR enrich in mucosa in cynomolgus monkeys.","authors":"Kelsie Marks, Nirav Shah, Ly Pham, Jun Chen, Ian White, Krista Burke, Peter Garrett, Mathieu Marella, Prathap Nagaraja Shastri, Brian Geist, Partha Chowdhury, Vinicius Carreira, Wan Cheung Cheung, Adam Zwolak","doi":"10.1080/19420862.2026.2743413","DOIUrl":"10.1080/19420862.2026.2743413","url":null,"abstract":"<p><p>Therapeutic antibodies have limited access to barrier‑protected compartments such as the brain, lung and gastric mucosa, and kidney lumen, constraining their effectiveness in many diseases. Approaches using a bispecific antibody that targets a transcytosing receptor such as the polymeric Ig receptor (pIgR) can result in significant enrichment of IgG-based therapeutics across from blood into mucosal or mucosal lining. The polymeric Ig receptor is expressed in epithelial layers in many tissues, but differences in expression patterns across species represent a challenge in validating preclinical <i>in vivo</i> models. Here, we compare RNA and protein expression across an array of human, cynomolgus monkey, and mouse tissues. We show that pIgR expression in cynomolgus monkeys is similar to expression in humans. We further evaluate the ability of pIgR-targeted bispecific antibodies to transcytose into lung and gastrointestinal mucosa in cynomolgus monkeys. We show that pIgR-targeted bispecific antibodies rapidly deplete from serum, while enriching 5-10-fold in bronchoalveolar lavage fluid compared to normal IgG antibodies. These results support the use of anti-pIgR bispecific antibodies to treat diseases requiring targeting in mucosal areas.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2743413"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110771","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":"Discovery and engineering of bispecific TCR-mimic antibodies targeting peptide-HLA complex.","authors":"Jennifer Watkins-Yoon, Wei-Cheng Lu, Elyse M Petrunak, Noah J Tubo, Sara Halmos, William McConaughy, Rodolfo Ciuffa, Cédric Weber, Simon Friedensohn, Sune Justesen, Marie Skovgaard, Rennard Rachel, Caity Goshert, Lucy Liu, Piotr Bobrowicz, Jeffrey J Molldrem, Dongxing Zha","doi":"10.1080/19420862.2026.2731282","DOIUrl":"10.1080/19420862.2026.2731282","url":null,"abstract":"<p><p>TCR-mimic (TCRm) antibodies represent a promising new frontier in cancer immunotherapy, enabling the targeting of intracellular targets previously considered undruggable with antibodies. We developed an integrated platform for generating human antibodies that mimic T-cell receptors (TCRs) and recognize peptide-HLA complexes with high specificity and affinity. These antibody binders were then engineered into highly potent bispecific antibodies capable of redirecting T cells to kill tumor cells. By leveraging high-quality pHLA immunogens, fully human transgenic mice, advanced single B-cell discovery, and whole proteome off-target screening (X-Scan) techniques, this end-to-end platform establishes a new benchmark in TCRm discovery. In this study, we highlight the successful identification and engineering of antibodies targeting the Wilms Tumor 1 (WT1) antigen, demonstrating superior performance compared to competitors' TCRm antibodies.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2731282"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956288","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":"Rapid expression of therapeutic antibodies in mammalian cells via mRNA transfection.","authors":"Thornwit Chavalparit, Craig Barry, Helen Gunter, Marianne Gillard, Timothy Mercer, Esteban Marcellin","doi":"10.1080/19420862.2025.2599584","DOIUrl":"10.1080/19420862.2025.2599584","url":null,"abstract":"<p><p>Messenger RNA (mRNA) has emerged as a powerful tool for protein expression in clinical settings, yet its potential as a platform for biologics manufacturing remains underexplored. Here, we evaluate transient mRNA transfection in Chinese hamster ovary (CHO) cells as a rapid and versatile system for protein production. Using reporter mRNAs, we optimize transfection efficiency and benchmark performance against industry-standard plasmid transfection and stable cell line methods. We demonstrate that co-transfection of heavy and light chain mRNAs enables the efficient synthesis, assembly and secretion of the monoclonal antibody bevacizumab with high fidelity. Compared to conventional approaches, mRNA transfection drives rapid and predictable protein expression, reducing cell incubation times and enabling sequential or conditional expression. These features highlight mRNA as a flexible and efficient platform for transient expression, providing a foundation for accelerating the development and manufacturing of biologics.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2599584"},"PeriodicalIF":7.3,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743260","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":"Expanding the horizons of cancer therapy with next-generation 4-1BB agonists: a review of molecular and clinical strategies to maximize efficacy and ensure safety.","authors":"Gihoon You, Jungwoo Choi, Chorong Yang, Sora Kim, JuYeun Jeon, Kyungjin Park, Yangsoon Lee, Sang Hoon Lee","doi":"10.1080/19420862.2026.2622746","DOIUrl":"10.1080/19420862.2026.2622746","url":null,"abstract":"<p><p>Driven by the substantial limitations of first generation 4-1BB agonists urelumab and utomilumab, the field has shifted toward engineering next-generation molecules with improved therapeutic windows. This review provides a comprehensive analysis of this evolution, detailing how key molecular design strategies are used to restrict 4-1BB activation to the tumor microenvironment. We summarize available clinical data, highlighting that 4-1BB bispecific antibodies exhibit superior antitumor efficacy and more favorable safety profiles compared with their monospecific predecessors. Furthermore, we discuss strong rationale for combination strategies, emphasizing how 4-1BB signaling provides the crucial costimulatory signal necessary to sustain durable anti-tumor responses. In summary, this review elucidates the scientific basis of antibody engineering aimed at improving safety and tumor-selective activation of 4-1BB agonists and outlines future directions for optimizing their clinical application in cancer immunotherapy.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"18 1","pages":"2622746"},"PeriodicalIF":7.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125526","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}