IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-01-16 DOI: 10.1080/19420862.2025.2453515

Silvia Crescioli, Shashi Jatiani, Lenny Moise

{"title":"With great power, comes great responsibility: the importance of broadly measuring Fc-mediated effector function early in the antibody development process.","authors":"Silvia Crescioli, Shashi Jatiani, Lenny Moise","doi":"10.1080/19420862.2025.2453515","DOIUrl":"10.1080/19420862.2025.2453515","url":null,"abstract":"The field of antibody therapeutics is rapidly growing, with over 210 antibodies currently approved or in regulatory review and ~ 1,250 antibodies in clinical development. Antibodies are highly versatile molecules that, with strategic design of their antigen-binding domain (Fab) and the domain responsible for mediating effector functions (Fc), can be used in a wide range of therapeutic indications. Building on many years of progress, the biopharmaceutical industry is now advancing innovative research and development by exploring new targets and new formats and using antibody engineering to fine-tune functions tailored to specific disease requirements. In addition to considering the target and the disease context, however, the unique features of each therapeutic antibody trigger a diverse set of Fc-mediated effector functions. To avoid unexpected results on safety and efficacy outcomes during the later stages of the development process, it is crucial to measure the impact of antibody design on Fc-mediated effector function early in the antibody development process. Given the breadth of effector functions antibodies can deploy and the close interplay between the antibody Fab and Fc functional domains, it is important to conduct a comprehensive evaluation of Fc-mediated functions using an array of antigen-specific biophysical and cell-mediated functional assays. Here, we review antibody and Fc receptor properties that influence Fc effector functions and discuss their implications on development of safe and efficacious antibody therapeutics.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2453515"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007984","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

Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-12 DOI: 10.1080/19420862.2025.2461191

Nilufer P Seth, Rui Xu, Matthew DuPrie, Amit Choudhury, Samuel Sihapong, Steven Tyler, James Meador, William Avery, Edward Cochran, Thomas Daly, Julia Brown, Laura Rutitzky, Lynn Markowitz, Sujatha Kumar, Traymon Beavers, Sayak Bhattacharya, Hsin Chen, Viraj Parge, Karen Price, Yang Wang, Siddharth Sukumaran, Yvonne Pao, Katie Abouzahr, Fiona Elwood, Jay Duffner, Sucharita Roy, Pushpa Narayanaswami, Jonathan J Hubbard, Leona E Ling

{"title":"Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties.","authors":"Nilufer P Seth, Rui Xu, Matthew DuPrie, Amit Choudhury, Samuel Sihapong, Steven Tyler, James Meador, William Avery, Edward Cochran, Thomas Daly, Julia Brown, Laura Rutitzky, Lynn Markowitz, Sujatha Kumar, Traymon Beavers, Sayak Bhattacharya, Hsin Chen, Viraj Parge, Karen Price, Yang Wang, Siddharth Sukumaran, Yvonne Pao, Katie Abouzahr, Fiona Elwood, Jay Duffner, Sucharita Roy, Pushpa Narayanaswami, Jonathan J Hubbard, Leona E Ling","doi":"10.1080/19420862.2025.2461191","DOIUrl":"10.1080/19420862.2025.2461191","url":null,"abstract":"Nipocalimab is a human immunoglobulin G (IgG)1 monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high specificity and high affinity at both neutral (extracellular) and acidic (intracellular) pH, resulting in the reduction of circulating IgG levels, including those of pathogenic IgG antibodies. Here, we present the molecular, cellular, and nonclinical characteristics of nipocalimab that support the reported clinical pharmacology and potential clinical application in IgG-driven, autoantibody- and alloantibody-mediated diseases. The crystal structure of the nipocalimab antigen binding fragment (Fab)/FcRn complex reveals its binding to a unique epitope on the IgG binding site of FcRn that supports the observed pH-independent high-binding affinity to FcRn. Cell-based and in vivo studies demonstrate concentration/dose- and time-dependent FcRn occupancy and IgG reduction. Nipocalimab selectively reduces circulating IgG levels without detectable effects on other adaptive and innate immune functions. In vitro experiments and in vivo studies in mice and cynomolgus monkeys generated data that align with observations from clinical studies of nipocalimab in IgG autoantibody- and alloantibody-mediated diseases.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2461191"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399502","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

Nanoscale warriors against viral invaders: a comprehensive review of Nanobodies as potential antiviral therapeutics. 对抗病毒入侵者的纳米战士：纳米抗体作为潜在抗病毒疗法的全面回顾。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-04-09 DOI: 10.1080/19420862.2025.2486390

Vaishali Verma, Nimisha Sinha, Abhavya Raja

{"title":"Nanoscale warriors against viral invaders: a comprehensive review of Nanobodies as potential antiviral therapeutics.","authors":"Vaishali Verma, Nimisha Sinha, Abhavya Raja","doi":"10.1080/19420862.2025.2486390","DOIUrl":"https://doi.org/10.1080/19420862.2025.2486390","url":null,"abstract":"Viral infections remain a significant global health threat, with emerging and reemerging viruses causing epidemics and pandemics. Despite advancements in antiviral therapies, the development of effective treatments is often hindered by challenges, such as viral resistance and the emergence of new strains. In this context, the development of novel therapeutic modalities is essential to combat notorious viruses. While traditional monoclonal antibodies are widely used for the treatment of several diseases, nanobodies derived from heavy chain-only antibodies have emerged as promising \"nanoscale warriors\" against viral infections. Nanobodies possess unique structural properties that enhance their ability to recognize diverse epitopes. Their small size also imparts properties, such as improved bioavailability, solubility, stability, and proteolytic resistance, making them an ideal class of therapeutics for viral infections. In this review, we discuss the role of nanobodies as antivirals against various viruses. Techniques used for developing nanobodies, delivery strategies are covered, and the challenges and opportunities associated with their use as antiviral therapies are discussed. We also offer insights into the future of nanobody-based antiviral research to support the development of new strategies for managing viral infections.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2486390"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811744","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

Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-03-05 DOI: 10.1080/19420862.2025.2470309

Yi Liu, Xinyi Chen, Theodore Evan, Benjamina Esapa, Alicia Chenoweth, Anthony Cheung, Sophia N Karagiannis

{"title":"Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age.","authors":"Yi Liu, Xinyi Chen, Theodore Evan, Benjamina Esapa, Alicia Chenoweth, Anthony Cheung, Sophia N Karagiannis","doi":"10.1080/19420862.2025.2470309","DOIUrl":"10.1080/19420862.2025.2470309","url":null,"abstract":"Folate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues render FRα an attractive target for biological therapies. Here we review the biological significance, expression distribution, and characteristics of FRα as a highly promising and now established therapy target. We discuss the ongoing development of FRα-targeting antibodies and antibody-drug conjugates (ADCs), the first of which has been approved for the treatment of ovarian cancer, providing the impetus for heightened research and therapy development. Novel insights into the tumor microenvironment, advances in antibody engineering to enhance immune-mediated effects, the emergence of ADCs, and several studies of anti-FRα agents combined with chemotherapy, targeted and immune therapy are offering new perspectives and treatment possibilities. Hence, we highlight key translational research and discuss several preclinical studies and clinical trials of interest, with an emphasis on agents and therapy combinations with potential to change future clinical practice.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2470309"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567272","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.

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

An antibody developability triaging pipeline exploiting protein language models. 利用蛋白质语言模型的抗体可开发性分级管道。

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

A novel in vitro serum stability assay for antibody therapeutics incorporating internal standards.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-03-17 DOI: 10.1080/19420862.2025.2479529

Yihan Li, Rosendo Villafuerte-Vega, Vikram M Shenoy, Heidi M Jackson, Yuting Wang, Karen E Parrish, Gary J Jenkins, Hetal Sarvaiya

{"title":"A novel in vitro serum stability assay for antibody therapeutics incorporating internal standards.","authors":"Yihan Li, Rosendo Villafuerte-Vega, Vikram M Shenoy, Heidi M Jackson, Yuting Wang, Karen E Parrish, Gary J Jenkins, Hetal Sarvaiya","doi":"10.1080/19420862.2025.2479529","DOIUrl":"10.1080/19420862.2025.2479529","url":null,"abstract":"Antibody-based therapeutics have demonstrated remarkable therapeutic benefit, but their susceptibility to biotransformation and degradation in the body can affect their safety, efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) profiles. In vitro stability assessments play a pivotal role in proactively identifying potential liabilities of antibody therapeutics prior to animal studies. Liquid chromatography-mass spectrometry (LC-MS)-based in vitro stability assays has been developed and adopted in the biopharmaceutical industry for the characterization of antibody-based therapeutics. However, these methodologies often overlook operational error and random variation during sample preparation and analysis, leading to inaccurate stability estimation. To address this limitation, we have developed an LC-MS-based in vitro serum stability assessment that incorporates two internal standards (ISs), National Institute of Standards and Technology monoclonal antibody (NISTmAb) and its crystallizable fragment (Fc), to improve assay performance. Our method involves three steps: incubation of antibody therapeutics along with an IS in biological matrices, affinity purification, and LC-MS analysis. The stability of 21 monoclonal or bispecific antibodies was assessed in serums of preclinical species using this method. Our results showed improved accuracy and precision of recovery calculations with the incorporation of ISs, enabling a more confident stability assessment even in the absence of biotransformation or aggregation. In vitro stability correlated with in vivo exposure, suggesting that this in vitro assay could serve as a routine screening tool to select and advance stable antibody therapeutic candidates for subsequent in vivo studies.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2479529"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649724","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

Online native hydrophobic interaction chromatography-mass spectrometry of antibody-drug conjugates. 抗体-药物偶联物的在线天然疏水相互作用色谱-质谱分析。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2024-12-25 DOI: 10.1080/19420862.2024.2446304

Trevor Kempen, Lance Cadang, Yuchen Fan, Kelly Zhang, Tao Chen, Bingchuan Wei

{"title":"Online native hydrophobic interaction chromatography-mass spectrometry of antibody-drug conjugates.","authors":"Trevor Kempen, Lance Cadang, Yuchen Fan, Kelly Zhang, Tao Chen, Bingchuan Wei","doi":"10.1080/19420862.2024.2446304","DOIUrl":"https://doi.org/10.1080/19420862.2024.2446304","url":null,"abstract":"Hydrophobic interaction chromatography (HIC) is commonly used to determine the drug-to-antibody ratio (DAR) and drug load distribution of antibody-drug conjugates (ADCs). However, identifying various DAR species separated by HIC is challenging due to the traditional use of mobile phases that are incompatible with mass spectrometry (MS). Existing approaches used to couple HIC with MS often encounter issues, such as complex instrumentation, compromised separation efficiency, and reduced MS sensitivity. In this study, we introduce a 22-min online native HIC-MS method for the separation and characterization of different DAR species in ADCs, addressing these challenges. The key novelty of this method is the use of ammonium tartrate, a kosmotropic and thermally decomposable salt, as the salt of HIC mobile phase, ensuring both excellent HIC separation and MS compatibility. Additionally, an ultrashort size exclusion chromatography step is integrated for online sample cleaning, enhancing MS sensitivity. This platform native HIC-MS method offers a rapid, sensitive, and robust solution for comprehensive profiling of DAR species in ADCs with a simple and cost-effective instrumental setup.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2446304"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895850","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

Cost and supply considerations for antibody therapeutics. 抗体疗法的成本和供应考虑。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-01-19 DOI: 10.1080/19420862.2025.2451789

Chun Chen, Zoe Garcia, David Chen, Hong Liu, Piper Trelstad

引用次数: 0

Design of orthogonal constant domain interfaces to aid proper heavy/light chain pairing of bispecific antibodies.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-03-24 DOI: 10.1080/19420862.2025.2479531

Kyle A Barlow, Michael B Battles, Michael E Brown, Kaleigh Canfield, Xiaojun Lu, Heather Lynaugh, Morgan Morrill, C Garrett Rappazzo, Saira P Reyes, Chanita Sandberg, Beth Sharkey, Christin Strong, Jingfu Zhao, Arvind Sivasubramanian

{"title":"Design of orthogonal constant domain interfaces to aid proper heavy/light chain pairing of bispecific antibodies.","authors":"Kyle A Barlow, Michael B Battles, Michael E Brown, Kaleigh Canfield, Xiaojun Lu, Heather Lynaugh, Morgan Morrill, C Garrett Rappazzo, Saira P Reyes, Chanita Sandberg, Beth Sharkey, Christin Strong, Jingfu Zhao, Arvind Sivasubramanian","doi":"10.1080/19420862.2025.2479531","DOIUrl":"10.1080/19420862.2025.2479531","url":null,"abstract":"The correct pairing of cognate heavy and light chains is critical to the efficient manufacturing of IgG-like bispecific antibodies (bsAbs) from a single host cell. We present a general solution for the elimination of heavy chain (HC):light chain (LC) mispairs in bsAbs with <math><mi>κ</mi></math> LCs via the use of two orthogonal constant domain (CH1:C<math><mi>κ</mi></math>) interfaces comprising computationally designed amino acid substitutions. Substitutions were designed by Rosetta to introduce novel hydrogen bond (H-bond) networks at the CH1:C<math><mi>κ</mi></math> interface, followed by Rosetta energy calculations to identify designs with enhanced pairing specificity and interface stability. Our final design, featuring a total of 11 amino acid substitutions across two Fab constant regions, was tested on a set of six IgG-like bsAbs featuring a diverse set of unmodified human antibody variable domains. Purity assessments showed near-complete elimination of LC mispairs, including in cases with high baseline mispairing with wild-type constant domains. The engineered bsAbs broadly recapitulated the antigen-binding and biophysical developability properties of their monospecific counterparts and no adverse immunogenicity signal was identified by an in vitro assay. Fab crystal structures containing engineered constant domain interfaces revealed no major perturbations relative to the wild-type coordinates and validated the presence of the designed hydrogen bond interactions. Our work enables the facile assembly of independently discovered IgG-like bispecific antibodies in a single-cell host and demonstrates a streamlined and generalizable computational and experimental workflow for redesigning conserved protein:protein interfaces.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2479531"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692538","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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