IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/19420862.2025.2472009

James Sweet-Jones, Andrew C R Martin

引用次数: 0

Process development for production of non-originator NISTmAb from CHO and NS0 cell lines. 从CHO和NS0细胞系生产非起始源NISTmAb的工艺开发。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-05-22 DOI: 10.1080/19420862.2025.2505088

Erica J Fratz-Berilla, Nicole Azer, Xin Bush, JungHyun Kim, Casey Kohnhorst

{"title":"Process development for production of non-originator NISTmAb from CHO and NS0 cell lines.","authors":"Erica J Fratz-Berilla, Nicole Azer, Xin Bush, JungHyun Kim, Casey Kohnhorst","doi":"10.1080/19420862.2025.2505088","DOIUrl":"10.1080/19420862.2025.2505088","url":null,"abstract":"Cell lines that produce non-originator versions of the National Institute of Standards and Technology (NIST) monoclonal antibody reference material 8671 (NISTmAb) are invaluable to the biopharmaceutical industry because, unlike typical commercial cell lines, they can be used on a collaborative and noncompetitive basis for bioprocess development. NIST has generated NS0 clones, NISTCHO research-grade test material 10197 and reference material 8675 NISTCHO to fill this need. We set out to optimize seed train procedures, media and feeding strategies, and stirred tank and rocking bioreactor processes to facilitate our studies on the effects of cell substrate and bioreactor process parameters on non-originator NISTmAb quality attributes. For two NS0 clones and NISTCHO, we improved the baseline methods for seed train culture and demonstrated the critical roles of agitation and gassing strategies for stirred-tank bioreactor operations. For NISTCHO we also tested fed-batch and perfusion processes in rocking bioreactors, identifying several critical process parameters and in-process controls. In this work, for the NIST NS0-59 and NS0-66 clones, we demonstrated that shake flask geometry was critical for culturing a highly viable seed train with a high growth rate and exhibited impacts of feeds, agitation, and gassing during initial bioreactor process development. We identified agitation rates and gassing strategy as critical process parameters for NISTCHO stirred-tank bioreactor operations and established processes for fed-batch and perfusion rocking bioreactor operations. We anticipate this work to benefit the growing number of researchers employing non-originator NISTmAb-expressing cell lines to support precompetitive innovation in biomanufacturing.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2505088"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128099","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}

引用次数: 0

Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features. 人抗体可变结构域种系的数据驱动分析：配对、序列和结构特征。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-05-25 DOI: 10.1080/19420862.2025.2507950

Clarissa A Seidler, Vera A Spanke, Jakob Gamper, Alexander Bujotzek, Guy Georges, Klaus R Liedl

{"title":"Data-driven analyses of human antibody variable domain germlines: pairings, sequences and structural features.","authors":"Clarissa A Seidler, Vera A Spanke, Jakob Gamper, Alexander Bujotzek, Guy Georges, Klaus R Liedl","doi":"10.1080/19420862.2025.2507950","DOIUrl":"10.1080/19420862.2025.2507950","url":null,"abstract":"The Observed Antibody Space provides the most abundant collection of annotated paired antibody variable domain sequences, thus offering a unique platform for the systematic investigation of the factors governing the pairing of antibody heavy and light chains. By examining a range of characteristics, including amino acid conservation, structural features, charge distribution, and interface residue identity, we challenge the prevailing assumption that pairing is random. Our findings indicate that specific physicochemical properties of single amino acid residues may influence the compatibility and affinity of heavy and light chain combinations. Further structural analyses based on antibody Fv fragments deposited in the Protein Data Bank (PDB) provide insights into the underlying structural features driving these pairing preferences, including a novel definition for the residues constituting the VH-VL interface, based on a collection of over 3500 structures. These results have significant implications for understanding antibody assembly and may guide the rational design of therapeutic antibodies with desired properties. Moreover, we provide a complete description and reference characterizing the various human germlines.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2507950"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142463","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}

引用次数: 0

CDR clipping-induced heterodimerization: identification of a novel dimerization mechanism in a co-formulated antibody cocktail via a multifaceted mass spectrometry approach. CDR剪切诱导的异二聚化：通过多面质谱方法鉴定共配制抗体鸡尾酒中的一种新的二聚化机制。

IF 7.3 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-08-14 DOI: 10.1080/19420862.2025.2546074

Andrew J Heindel, Yang Shen, Timothy N Tiambeng, Yuetian Yan, Shunhai Wang, Ning Li

{"title":"CDR clipping-induced heterodimerization: identification of a novel dimerization mechanism in a co-formulated antibody cocktail via a multifaceted mass spectrometry approach.","authors":"Andrew J Heindel, Yang Shen, Timothy N Tiambeng, Yuetian Yan, Shunhai Wang, Ning Li","doi":"10.1080/19420862.2025.2546074","DOIUrl":"10.1080/19420862.2025.2546074","url":null,"abstract":"Co-formulated antibody cocktails are becoming an increasingly popular therapeutic class; however, they present analytical challenges over traditional single monoclonal antibody (mAb) formulations. One paramount concern is the formation of heteromeric species that have unknown impacts on safety and efficacy. Consequently, effective approaches for identifying and characterizing high-molecular weight (HMW) impurities are critical to the successful development of this therapeutic class. In this study, we used a multifaceted mass spectrometry approach to characterize a unique dimer species formed between two co-formulated mAbs under thermal stress, revealing an intriguing dimerization mechanism that is driven by complementarity-determining region clipping-induced domain swap. Size exclusion chromatography-mass spectrometry, complemented by post-column denaturation, was utilized at both intact and subunit levels to pinpoint the dimerization interface. Additionally, by probing the disulfide bond susceptibility changes via limited reduction and middle-down analysis, the structural changes of the involved domains were studied. These results highlight the critical role of sophisticated analytical methods in comprehending and addressing the complexities linked to co-formulated mAb cocktails.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2546074"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855724","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}

引用次数: 0

Safety and tolerability of intramuscular sotrovimab administered at different injection sites: results from the Phase 1 COSMIC study. 在不同注射部位肌注sotrovimab的安全性和耐受性：来自一期COSMIC研究的结果

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-01-29 DOI: 10.1080/19420862.2025.2456467

Jennifer Moore, Alicia Aylott, Wen-Hung Chen, Jerzy Daniluk, Ian A Hawes, Sergio Parra, Prosenjit Sarkar, Yasmin Sanchez-Pearson, Megan Turner, Amanda Peppercorn, Andrew Skingsley

引用次数: 0

Immunogenicity of single-chain antibodies: germlining of a VHH lowers T-cell activation from epitopes in FR2 and CDR regions. 单链抗体的免疫原性：VHH的种衬降低了FR2和CDR区域表位的t细胞活化。

IF 7.3 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-10-12 DOI: 10.1080/19420862.2025.2571406

Remi Giraudet, Adrien Laroche, Benjamin Chalopin, Steven Dubois, Evelyne Correia, Isabelle Staropoli, Olivier Schwartz, Bernard Maillère, Hervé Nozach

{"title":"Immunogenicity of single-chain antibodies: germlining of a VHH lowers T-cell activation from epitopes in FR2 and CDR regions.","authors":"Remi Giraudet, Adrien Laroche, Benjamin Chalopin, Steven Dubois, Evelyne Correia, Isabelle Staropoli, Olivier Schwartz, Bernard Maillère, Hervé Nozach","doi":"10.1080/19420862.2025.2571406","DOIUrl":"https://doi.org/10.1080/19420862.2025.2571406","url":null,"abstract":"Single-chain antibodies (scAbs), derived from camelid antibodies, have gained attention as therapeutic candidates due to their small size and perceived low immunogenicity, but recent studies have reported immune responses to several scAbs. To better understand their immunogenicity, we investigated the T-cell responses induced by VHH76, a VHH-Fc engineered to target the SARS-CoV-2 RBD, along with its humanized and germlined variants. The humanized variant contains six human substitutions, while the germlined variant was obtained by screening of a combinatorial library of the VHH76 sequences, comprising human and wild-type substitutions at 12 different positions. The germlined variant finally contains 16 human substitutions. All VHH76 variants triggered CD4 T-cell responses from healthy donors, with the germlined VHH76 showing significantly reduced T-cell stimulation. Two epitope regions were identified: one overlapping CDR3 and another spreading from CDR1 to CDR2. Additional human substitutions at the VHH-conserved positions in FR2 compromised the biological properties of the germlined VHH76 and did not seem to reduce clearly the risk of T-cell response. In conclusion, using a sensitive T-cell assay, we showed that T cells specific for VHH76 variants were detected in the blood of healthy donors and that the frequency of responding T cells diminished with germlining. While epitopes in CDR3 are linked to VHH76 specificity, modifying the conserved FR2 region presents challenges for reducing VHH76 immunogenicity. This study contributes to the understanding of VHH76 immunogenicity and offers insights into strategies to mitigate immune responses.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2571406"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280512","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}

引用次数: 0

Computational analysis reveals non-consensus N-glycosylation sequons in antibody Fab region.

IF 7.3 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1080/19420862.2025.2574406

Baiyu Qiu, Edwin Chen, Tawnya Flick, Simon Letarte

{"title":"Computational analysis reveals non-consensus N-glycosylation sequons in antibody Fab region.","authors":"Baiyu Qiu, Edwin Chen, Tawnya Flick, Simon Letarte","doi":"10.1080/19420862.2025.2574406","DOIUrl":"https://doi.org/10.1080/19420862.2025.2574406","url":null,"abstract":"Protein glycosylation at asparagine typically occurs at a consensus motif. However, recent studies have reported instances of N-glycosylation at non-consensus sites, though the mechanisms and implications of these atypical modifications remain unclear. In this study, we identified novel non-consensus N-glycosylation motifs with low glycosylation occupancy in the Fab region of human antibodies. We developed a computational workflow to predict the interaction between non-consensus peptides and the eukaryotic oligosaccharyltransferase (OST) complex. This model was validated through site-directed mutagenesis around the asparagine residue and glycosylation quantification via mass spectrometry. Our results show that glycan occupancy at non-consensus sites can be modulated by mutations that influence OST binding affinity. Pharmacological inhibition of OST activity reduced non-consensus and consensus glycosylation in both Fab and Fc regions. Additionally, we identified new non-consensus glycosylation sites in natural human antibodies, revealing the sequence preferences governing these modifications. These findings provide mechanistic insights into OST sequence specificity and establish a computational and analytical framework for assessing atypical N-glycosylation, aiding glycan profile control in therapeutic antibody development.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2574406"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292646","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}

引用次数: 0

Integrating immune library probing with structure-based computational design to develop potent neutralizing nanobodies against emerging SARS-CoV-2 variants. 将免疫文库探测与基于结构的计算设计相结合，开发针对新出现的SARS-CoV-2变体的有效中和纳米体。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-05-06 DOI: 10.1080/19420862.2025.2499595

Lidia Cerdán, Katixa Silva, Daniel Rodríguez-Martín, Patricia Pérez, María A Noriega, Ana Esteban Martín, Alfonso Gutiérrez-Adán, Yago Margolles, Juan A Corbera, Miguel A Martín-Acebes, Juan García-Arriaza, Juan Fernández-Recio, Luis A Fernández, José M Casasnovas

{"title":"Integrating immune library probing with structure-based computational design to develop potent neutralizing nanobodies against emerging SARS-CoV-2 variants.","authors":"Lidia Cerdán, Katixa Silva, Daniel Rodríguez-Martín, Patricia Pérez, María A Noriega, Ana Esteban Martín, Alfonso Gutiérrez-Adán, Yago Margolles, Juan A Corbera, Miguel A Martín-Acebes, Juan García-Arriaza, Juan Fernández-Recio, Luis A Fernández, José M Casasnovas","doi":"10.1080/19420862.2025.2499595","DOIUrl":"https://doi.org/10.1080/19420862.2025.2499595","url":null,"abstract":"To generate antibodies (Abs) against SARS-CoV-2 emerging variants, we integrated multiple tools and engineered molecules with excellent neutralizing breadth and potency. Initially, the screening of an immune library identified a nanobody (Nb), termed Nb4, specific to the receptor-binding domain (RBD) of the Omicron BA.1 variant. A Nb4-derived heavy chain antibody (hcAb4) recognized the spike (S) of the Wuhan, Beta, Delta, Omicron BA.1, and BA.5 SARS-CoV-2 variants. A high-resolution crystal structure of the Nb4 variable (VHH) domain in complex with the SARS-CoV-2 RBD (Wuhan) defined the Nb4 binding mode and interface. The Nb4 VHH domain grasped the RBD and covered most of its outer face, including the core and the receptor-binding motif (RBM), which was consistent with hcAb4 blocking RBD binding to the SARS-CoV-2 receptor. In mouse models, a humanized hcAb4 showed therapeutic potential and prevented the replication of SARS-CoV-2 BA.1 virus in the lungs of the animals. In vitro, hcAb4 neutralized Wuhan, Beta, Delta, Omicron BA.1, and BA.5 viral variants, as well as the BQ.1.1 subvariant, but showed poor neutralization against the Omicron XBB.1.5. Structure-based computation of the RBD-Nb4 interface identified three Nb4 residues with a reduced contribution to the interaction with the XBB.1.5 RBD. Site-saturation mutagenesis of these residues resulted in two hcAb4 mutants with enhanced XBB.1.5 S binding and virus neutralization, further improved by mutant Nb4 trimers. This research highlights an approach that combines library screening, Nb engineering, and structure-based computational predictions for the generation of SARS-CoV-2 Omicron-specific Abs and their adaptation to emerging variants.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2499595"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979006","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}

引用次数: 0

Leveraging multi-modal feature learning for predictions of antibody viscosity. 利用多模态特征学习预测抗体黏度。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-04-11 DOI: 10.1080/19420862.2025.2490788

Krishna D B Anapindi, Kai Liu, Willie Wang, Yao Yu, Yan He, Edward J Hsieh, Ying Huang, Daniela Tomazela

{"title":"Leveraging multi-modal feature learning for predictions of antibody viscosity.","authors":"Krishna D B Anapindi, Kai Liu, Willie Wang, Yao Yu, Yan He, Edward J Hsieh, Ying Huang, Daniela Tomazela","doi":"10.1080/19420862.2025.2490788","DOIUrl":"https://doi.org/10.1080/19420862.2025.2490788","url":null,"abstract":"The shift toward subcutaneous administration for biologic therapeutics has gained momentum due to its patient-friendly nature, convenience, reduced healthcare burden, and improved compliance compared to traditional intravenous infusions. However, a significant challenge associated with this transition is managing the viscosity of the administered solutions. High viscosity poses substantial development and manufacturability challenges, directly affecting patients by increasing injection time and causing pain at the injection site. Furthermore, high viscosity formulations can prolong residence time at the injection site, affecting absorption kinetics and potentially altering the intended pharmacological profile and therapeutic efficacy of the biologic candidate. Here, we report the application of a multimodal feature learning workflow for predicting the viscosity of antibodies in therapeutics discovery. It integrates multiple data sources including sequence, structural, physicochemical properties, as well as embeddings from a language model. This approach enables the model to learn from various underlying rules, such as physicochemical rules from molecular simulations and protein evolutionary patterns captured by large, pre-trained deep learning models. By comparing the effectiveness of this approach to other selected published viscosity prediction methods, this study provides insights into their intrinsic viscosity predictive potential and usability in early-stage therapeutics antibody development pipelines.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2490788"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971334","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}

引用次数: 0

Development and characterization of AD-214, an anti-CXCR4 i-body-Fc fusion for the treatment of idiopathic pulmonary fibrosis. AD-214是一种抗cxcr4 i-body-Fc融合治疗特发性肺纤维化的药物。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1080/19420862.2025.2505090

Jason P Lynch, Louise Organ, Khamis Tomusange, Lukasz Kowalczyk, Dallas J Hartman, Angus Tester, Chris Hosking, Michael Foley

{"title":"Development and characterization of AD-214, an anti-CXCR4 i-body-Fc fusion for the treatment of idiopathic pulmonary fibrosis.","authors":"Jason P Lynch, Louise Organ, Khamis Tomusange, Lukasz Kowalczyk, Dallas J Hartman, Angus Tester, Chris Hosking, Michael Foley","doi":"10.1080/19420862.2025.2505090","DOIUrl":"10.1080/19420862.2025.2505090","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by scarring and tissue remodeling. Current treatments have limited efficacy and significant side effects. To address these limitations, we developed AD-214, an anti-CXCR4-Fc-fusion protein composed of an anti-CXCR4 i-body (AD-114) tethered at its C terminus to constant domains 2 and 3 of the Fc region of a mutated human IgG1 lacking effector function. AD-214 binds with high affinity and specificity to CXCR4, modulates intracellular signaling, and inhibits key fibrotic pathways. Using fibrosis models, we demonstrate that AD-214 treatment significantly reduces collagen deposition and lung remodeling and has a unique mode of action. In Phase 1 clinical trials, intravenous infusion of AD-214 led to high and sustained CXCR4 receptor occupancy (RO), but whether RO and efficacy are causally linked remained to be determined. Herein, we demonstrate that CXCR4 RO by AD-214 inhibits primary human leukocyte migration, a model fibrotic process, and that migration inhibition is achievable at concentrations of AD-214 present in the serum of healthy human volunteers administered AD-214. Taken together, these data provide proof of concept for AD-214 as a novel treatment strategy for IPF and suggest that clinically feasible dosing regimens may be efficacious.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2505090"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111240","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}

引用次数: 0

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