Antibody Therapeutics最新文献

{"title":"Discovery of candidate antibodies and antigens for acute myeloid leukemia therapy by combining whole-cell phage display selection and CRISPR-Cas9 library screening.","authors":"Koji Hashimoto, Verena Konetzki, Andoni Garitano-Trojaola, Sabrina Kraus, Sabrina R Friedel, Michael Hudecek, Haiyong Peng, Christoph Rader","doi":"10.1093/abt/tbag043","DOIUrl":"https://doi.org/10.1093/abt/tbag043","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) remains challenging to treat and often requires intensive chemotherapy. In contrast to other hematologic malignancies, the development of effective antibody-based and cellular immunotherapies for AML has been limited by the scarcity of suitable target antigens.</p><p><strong>Methods: </strong>We applied a phage display-based whole-cell panning method in which Fab-phage were biotinylated and captured, followed by next-generation sequencing (NGS), bioinformatic, and statistical analyses. Target deconvolution was performed using a CRISPR-Cas9 knockout library, fluorescence-activated cell sorting of antigen-negative cells, and NGS-based gRNA analysis. Selected candidates were further evaluated using primary AML patient cells and chimeric antigen receptor (CAR)-T cell assays.</p><p><strong>Results: </strong>We identified 28 unique monoclonal antibodies that preferentially bound AML cell lines. CRISPR-Cas9-based target deconvolution enabled efficient identification of three cognate antigens. Selected lead candidates were validated by staining primary cells from AML patients and were engineered into CAR constructs. CAR-T cells targeting the identified antigens mediated efficient eradication of AML cell lines and primary AML cells.</p><p><strong>Conclusions: </strong>This integrated antibody-based antigen discovery and validation approach may accelerate the development of monoclonal antibody- and CAR-based immunotherapies for AML and other indications.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"576-594"},"PeriodicalIF":4.8,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A landscape of sequence variants in 51 commercial antibody therapeutics.","authors":"Gangling Xu, Gang Wu, Chunbo Cui, Sihan Wei, Maoqing Duan, Yongfei Cui, Yu Ting Mei, Chuanfei Yu, Lan Wang","doi":"10.1093/abt/tbag048","DOIUrl":"https://doi.org/10.1093/abt/tbag048","url":null,"abstract":"<p><strong>Background: </strong>Sequence variants (SVs), unintended amino acid substitutions, represent a quality attribute of antibody therapeutics with potential safety and efficacy implications. Although control strategies are evolving, a comprehensive landscape of SVs in commercial antibody products, including biosimilars, innovators, and those from different expression systems or geographical origins, remains largely unexplored.</p><p><strong>Methods: </strong>We systematically analyzed SVs in 51 commercial antibody therapeutics via optimized high-sensitivity LC-MS/MS peptide mapping. The panel encompassed originators and biosimilars from Chinese and multinational firms, eukaryotic (CHO, NS0) and prokaryotic (<i>Escherichia coli</i>) expression systems, and diverse formats (mAbs, bispecifics, ADCs) and subclasses (IgG1, IgG2, IgG4).</p><p><strong>Results: </strong>Across all products, 3006 SV occurrences were identified. The vast majority (92.5%) were ≤0.1% per site. Only 7.5% (226 SV occurrences) exceeded 0.1%, 2.4% (72 SV occurrences) exceeded 0.2%, and a minimal 0.4% (12 SV occurrences) exceeded 0.5%. SV levels of Chinese biosimilars and innovators were comparable to international counterparts. While prokaryotic-derived products showed more SVs above 0.2%, SV levels showed no significant correlation with antibody subclasses or formats. Batch-to-batch consistency was excellent across all products.</p><p><strong>Conclusions: </strong>This study provides the largest empirical SV dataset for marketed antibody therapeutics to date. It demonstrates manufacturing processes maintain SV levels below 0.2% per site and reveals no inherent SV disparity across product origin, subclass, or format. Empirically, this 0.2% threshold serves as a pragmatic benchmark for commercial antibody quality control. These findings provide a science-based reference for establishing cell line screening in-process limits, refining industrial SV control strategies, and guiding regulatory science.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"595-605"},"PeriodicalIF":4.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrahigh-DAR antibody-drug conjugates: advancing the next generation of targeted therapy.","authors":"Haosheng Feng, Bin Liu","doi":"10.1093/abt/tbag042","DOIUrl":"https://doi.org/10.1093/abt/tbag042","url":null,"abstract":"<p><p>Conventional antibody-drug conjugates (ADCs) are typically limited to drug-to-antibody ratios (DARs) of ≤8 because of restricted conjugation sites and unfavorable physicochemical properties at higher DARs, including increased hydrophobicity, aggregation, and rapid systemic clearance. Consequently, most clinically approved ADCs rely on highly potent cytotoxic payloads (e.g. IC₅₀ < 1 nM), which can result in significant off-target toxicities. This mini-review summarizes recent advances in next-generation ultrahigh-DAR antibody therapeutics, with a particular focus on two emerging platforms: antibody polymer conjugates (APCs) and antibody-nanoparticle conjugates (ANCs). We discuss their design principles, structural features, and strategies for achieving high payload loading while preserving antigen recognition and favorable pharmacokinetic properties. Recent advances in APCs and ANCs demonstrate that polymer and nanomaterial engineering can overcome the conventional DAR limitations of ADCs, enabling substantially greater payload loading per targeting antibody without compromising targeting performance. These ultrahigh-DAR platforms also expand the range of deliverable payloads, facilitating the development of therapeutics with diverse mechanisms of action beyond traditional ultrapotent cytotoxic agents. Ultrahigh-DAR antibody therapeutics represent a promising next generation of targeted drug delivery systems. By integrating advances in polymer and nanomaterial engineering, APCs and ANCs have the potential to broaden the therapeutic landscape of antibody-based medicines and enable safer, more effective targeted therapies across a wide range of diseases.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"566-575"},"PeriodicalIF":4.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An IgG-like fusion protein comprising an anti-spike S2 antibody and ACE2 exhibits potent and broad neutralization against SARS-CoV-2 and variants of concern.","authors":"Zhizhong Wei, Ximing Liu, Kailun Wang, Lan Chen, Xia Xiao, Yinyan Sun, Wei Wang, Yizhe Chen, Linqiang Fang, Yonghe Qi, Fang Yang, Xinyan Hao, Ruihua Fan, Sanduo Zheng, Lili Ren, Wenhui Li, Xinxin Tian, Jianhua Sui","doi":"10.1093/abt/tbag041","DOIUrl":"https://doi.org/10.1093/abt/tbag041","url":null,"abstract":"<p><strong>Background: </strong>The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the value of broad-spectrum antiviral strategies. Antibody-engineering approaches targeting conserved regions of the Spike protein may enhance neutralizing potency and breadth.</p><p><strong>Methods: </strong>A human antibody (P23) against the Spike protein of SARS-CoV-2 was identified using a human antibody phage display library panning and screening for binding affinity and breadth against multiple coronavirus Spike proteins using surface plasmon resonance (SPR). The epitope of P23 was characterized using the S1 and S2 subunits of SARS-CoV-2 Spike protein and hydrogen-deuterium exchange mass spectrometry (HDX-MS). An IgG-like bispecific fusion protein (Bs-ACE2-P23) was engineered by fusing the extracellular domain (ECD) of human angiotensin-converting enzyme 2 (ACE2) to the N-terminus of the P23 heavy chain (HC). Neutralizing activity was evaluated against both pseudotyped and authentic SARS-CoV-2 variants.</p><p><strong>Results: </strong>P23 cross-bound Spike proteins from SARS-CoV-2 wild type (WT), D614G and JN.1 variants, Pangolin-CoV, Bat coronavirus RaTG13, and SARS-CoV-1, recognizing an epitope on the S2 subunit adjacent to the fusion peptide (FP). While P23 was ineffective against D614G-containing SARS-CoV-2 variants, Bs-ACE2-P23 exhibited markedly enhanced neutralization potency. This bispecific architecture also improved the neutralizing activity of another FP-targeting antibody.</p><p><strong>Conclusion: </strong>We developed a bispecific fusion protein with potent broad-spectrum neutralizing activity against SARS-CoV-2 variants. This architecture provides a promising strategy for next-generation coronavirus biologics.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"550-565"},"PeriodicalIF":4.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOTAM-TCB: Universal Small Molecule-guided Hapten- and T Cell-bispecific Antibodies for Cancer Immunotherapy.","authors":"Marlena Surowka, Theresa Kober, Daniela Matscheko, Andreas Ehler, Wilson Macedo, Denis Assisi, John Challier, Andrzej Sobieniecki, Reto Gianotti, Ali Bransi, Johannes Sam, Juan José Bonfiglio, Moreno Wichert, Antonio Ricci, Joerg Benz, Pablo Umaña, Dario Venetz, Christian Klein","doi":"10.1093/abt/tbag038","DOIUrl":"https://doi.org/10.1093/abt/tbag038","url":null,"abstract":"<p><strong>Background: </strong>Tumor heterogeneity has been identified as a major roadblock for cancer immunotherapy. To overcome this, universal effector cell engagers with interchangeable tumor-targeting adaptors have been developed. Current concepts in this field consist of antibody-based adaptors. Small-molecule (SM) ligands, on the other hand, infiltrate tissues rapidly, have short half-lives, and are potentially orally available. Therefore, we hypothesized that utilizing SM adaptors, combined with effector antibodies, could represent an attractive off-the-shelf therapy.</p><p><strong>Methods: </strong>Here, we introduce the development of target-agnostic, small-molecule-guided hapten- and T cell-bispecific (TCB) antibodies with high affinity between the adaptor-effector pair. Specifically, we designed SM adaptors based on known tumor-targeting ligands with specificity to the antigens folate receptor 1 (FOLR1), prostate-specific membrane antigen (PSMA) and carbonic anhydrase IX (CAIX), and conjugated them to Ca²⁺-loaded 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (DOTAM) as a hapten. As an effector antibody, we designed DOTAM-specific T cell bispecific antibodies (DOTAM-TCB) with femtomolar (fM) affinity for the hapten.</p><p><strong>Results: </strong><i>In vitro</i> experiments showed in-solution assembly of stable adaptor-effector complexes. Additionally, T cell-mediated tumor killing was initiated by the universal DOTAM-TCB when combined with adaptors across various tumor cells. <i>Ex vivo</i> study of CAIX-directed Ca-DOTAM-acetazolamide (Ca-DOTAM-AAZ) with DOTAM-TCB showed potent activation of T cells against murine-engrafted human HT-29 tumor.</p><p><strong>Conclusions: </strong>The studies described here demonstrate proof-of-concept for using hapten-containing small molecules as adaptors for effective universal T cell engager-based cancer immunotherapy.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"535-549"},"PeriodicalIF":4.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hinge-region Cys-to-Ser mutation enables homogeneous DAR6 anti-c-Met biparatopic ADCs with tolerable O-glycosylation.","authors":"Deyong Song, Zhenduo Shen, Xiaolin Zhu, Haifeng Zhao, Yingdi Wang, Junmei Zhang, Rui Li, Hongguang Xu, Zengjin Cheng, Xiaoju Ma, Haixia Lin, Changlin Dou, Min Xiao","doi":"10.1093/abt/tbag040","DOIUrl":"https://doi.org/10.1093/abt/tbag040","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugates (ADCs) with homogeneous drug-to-antibody ratios (DARs) are increasingly favored for their improved physicochemical and pharmacokinetic properties; however, strategies to reliably generate homogeneous DAR6 ADCs remain limited.</p><p><strong>Methods: </strong>In this study, we investigate hinge-region cysteine engineering as an approach to constrain conjugation stoichiometry, using a potent biparatopic anti-c-Met antibody as a model. Various biological and physicochemical assays were used for its characterization.</p><p><strong>Results: </strong>We show that substitution of a hinge-region cysteine within a CPPC (Cysteine - Proline - Proline - Cysteine) motif reduces the number of accessible conjugation sites, allowing reproducible generation of homogeneous DAR6 ADCs. During characterization of Ser- or Thr-substituted hinge variants, we observed additional mass species consistent with mucin-type O-linked glycosylation. Site-specific mass spectrometry analyses localized these modifications to a serine residue within hinge-region and identified the core structures of the <i>O</i>-glycans. Analysis of additional antibodies carrying analogous mutations demonstrated that hinge-associated O-glycosylation is not restricted to a single antibody scaffold.</p><p><strong>Conclusions: </strong>These results demonstrate that hinge-region cysteine engineering can serve as a rational and adaptable approach for DAR6 ADC development while highlighting the need for case-by-case evaluation of associated post-translational modifications during antibody engineering.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"521-534"},"PeriodicalIF":4.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond affinity: AI-supported developability assessment and multi-objective optimization in antibody development.","authors":"Qianhui Jiang, Jiahui Guan, Dan Yu, Pradeep Singh, George Pelekos, Edward Chin Man Lo, Junwen Wang","doi":"10.1093/abt/tbag039","DOIUrl":"https://doi.org/10.1093/abt/tbag039","url":null,"abstract":"<p><p>Therapeutic antibodies are a major class of medicines, but high target affinity alone does not ensure manufacturability, stability, safety, or clinical success. Developability has therefore become a central constraint in antibody engineering and has pushed the field beyond affinity-first screening toward multi-objective decision-making. Machine-learning-based models increasingly integrate antibody sequence, structure, interaction, and assay data to estimate properties such as affinity, specificity, aggregation, viscosity, solubility, stability, immunogenicity, and pharmacokinetics before experimental testing. In practice, these models are most useful when they help prioritize experiments rather than replace empirical evaluation. Here, we review the data resources used for antibody developability modeling, the main classes of property predictors, and optimization frameworks that balance competing design objectives. We cover Pareto optimization, Bayesian optimization, active learning, and conditional generative modeling, and discuss how these approaches are being adapted to bispecific antibodies and nanobodies. We argue that AI is most useful when model outputs are interpreted in the context of assay design, uncertainty, and antibody format, and when they are used to guide candidate selection and experimental design rather than serve as stand-alone surrogates for developability.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 4","pages":"508-520"},"PeriodicalIF":4.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformational epitope engagement by anti-MSLN ADC RC88 confers resistance to soluble mesothelin.","authors":"Yidan Xu, Mingyang Li, Lili Wang, Kailin Wang, Xiao Wang, Xiaoping Zhang, Zhanjiao Yu, Yinghao Xin, Chenglin He, Xiangyi He, Jing Zhou, Xiaoshan Min, Hang Chen, Zhulun Wang, Dong Li, Jianmin Fang, Yuanhao Li","doi":"10.1093/abt/tbag036","DOIUrl":"10.1093/abt/tbag036","url":null,"abstract":"<p><strong>Background: </strong>Mesothelin (MSLN) is a therapeutic target for antibody-drug conjugates (ADCs) due to its tumor-selective overexpression. However, soluble MSLN (sMSLN) in circulation compromises efficacy by acting as a decoy. RC88 is a clinical-stage ADC composed of a humanized anti-MSLN antibody conjugated to a monomethyl auristatin E (MMAE) payload. This study elucidates the unique binding mechanism that allows RC88 to maintain superior efficacy despite sMSLN interference.</p><p><strong>Methods: </strong>We characterized the RC88-MSLN interaction via structural analysis and mutagenesis. The impact of sMSLN on binding was assessed using competitive cellular assays. In vitro internalization kinetics and cytotoxicity were evaluated to determine the therapeutic potential.</p><p><strong>Results: </strong>RC88 targets a high-affinity N-terminal epitope overlapping the MUC16/CA125-binding site, competitively inhibiting this interaction. Notably, due to the structural flexibility of MSLN, RC88 also engages a secondary, low affinity juxtamembrane epitope at the C-terminus. This conformational binding confers resistance to sMSLN interference and enhanced tumor cell retention. <i>In vitro</i>, RC88-ADC maintained near-complete cytotoxic potency even in the presence of physiologically relevant sMSLN concentrations. <i>In vivo</i>, RC88 suppressed tumor growth in ovarian cancer xenografts.</p><p><strong>Conclusion: </strong>Our findings demonstrate that RC88 utilizes a novel conformational binding strategy to overcome the limitations of soluble antigen interference. These findings provide a mechanistic rationale for the encouraging clinical activity of RC88 and suggest that conformational epitope targeting represents a promising strategy for overcoming sMSLN interference in MSLN-positive cancers.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 3","pages":"460-470"},"PeriodicalIF":4.8,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fully human antagonistic antibodies targeting FPR2 through dual extracellular-loop engagement for gastric cancer therapy.","authors":"Min Su Kim, Tae Hyun Kang","doi":"10.1093/abt/tbag035","DOIUrl":"10.1093/abt/tbag035","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a major cause of cancer mortality worldwide, particularly in metastatic stages. N-formyl peptide receptor 2 (FPR2), a class A G protein-coupled receptor activated by the <i>Helicobacter pylori</i>-derived peptide Hp(2-20), promotes GC progression by stimulating oncogenic signaling pathways. However, no clinically applicable agents selectively targeting FPR2 have been developed.</p><p><strong>Methods: </strong>We generated fully human antagonistic antibodies targeting FPR2 using a two-step discovery strategy. A CDR-H3-focused synthetic single-chain variable fragment library was screened against an extracellular loop 3 (ECL3) peptide, followed by light-chain engineering to confer dual engagement of extracellular loop 2 (ECL2).</p><p><strong>Results: </strong>The engineered antibody exhibited dose-dependent binding to both ECL2 and ECL3 peptides, selectively recognized FPR2 over other FPR family members, and showed nanomolar binding to FPR2-expressing cancer cells. The antibody inhibited Hp(2-20)-induced calcium mobilization and suppressed migration and invasion of Adenocarcinoma Gastric (AGS) gastric cancer cells. Structural modeling indicated a lid-like binding mode occluding the orthosteric pocket.</p><p><strong>Conclusions: </strong>We developed a fully human antagonistic antibody that selectively binds and inhibits FPR2 through dual extracellular-loop engagement. The antibody potentially suppresses FPR2-driven signaling and invasive behaviors in gastric cancer cells, supporting its development for therapeutic application. Further assessment of its efficacy <i>in vivo</i> is warranted.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 3","pages":"449-459"},"PeriodicalIF":4.8,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery devices and container closure systems for co-formulated and co-administered biologics.","authors":"Ming Zhou, Kevin Duffy, Chris Mitchener, Galen Huaiqiu Shi, David Collins","doi":"10.1093/abt/tbag034","DOIUrl":"10.1093/abt/tbag034","url":null,"abstract":"<p><p>The rapid evolution of antibody-based biologics is transforming the management of chronic conditions and driving innovation in drug-delivery devices and container closure systems (CCS). Combination therapy enabled through coformulation or coadministration offers the potential for synergistic outcomes that are not achievable with single-drug products. This review examines development pathways and emerging strategies for delivery devices and CCS that support antibody-biologic coformulations and coadministration, from clinical trials through commercialization. We evaluate established technologies with an emphasis on design and delivery mechanisms, and on key technical considerations, including compatibility with dual-molecule formulations, protein-protein interactions, sterilization approaches, container closure integrity, and human factors in CCS and device design. We also highlight emerging technologies and future opportunities for advancement. Overall, this review provides insights into the challenges and innovations shaping CCS and delivery systems for co-formulated or co-administered antibody biologics.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"9 3","pages":"437-448"},"PeriodicalIF":4.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}