IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-01-09 DOI: 10.1080/19420862.2024.2439988

Andrew Maier, Minjeong Cha, Sean Burgess, Amy Wang, Carlos Cuellar, Soo Kim, Neeraja Sundar Rajan, Josephine Neyyan, Rituparna Sengupta, Kelly O'Connor, Nicole Ott, Ambrose Williams

{"title":"Predicting purification process fit of monoclonal antibodies using machine learning.","authors":"Andrew Maier, Minjeong Cha, Sean Burgess, Amy Wang, Carlos Cuellar, Soo Kim, Neeraja Sundar Rajan, Josephine Neyyan, Rituparna Sengupta, Kelly O'Connor, Nicole Ott, Ambrose Williams","doi":"10.1080/19420862.2024.2439988","DOIUrl":"10.1080/19420862.2024.2439988","url":null,"abstract":"In early-stage development of therapeutic monoclonal antibodies, assessment of the viability and ease of their purification typically requires extensive experimentation. However, the work required for upstream protein expression and downstream purification development often conflicts with timeline pressures and material constraints, limiting the number of molecules and process conditions that can reasonably be assessed. Recently, high-throughput batch-binding screen data along with improved molecular descriptors have enabled development of robust quantitative structure-property relationship (QSPR) models that predict monoclonal antibody chromatographic binding behavior from the amino acid sequence. Here, we describe a QSPR strategy for in silico monoclonal antibody purification process fit assessment. Principal Component Analysis is applied to extract a one-dimensional basis for comparison of molecular chromatographic binding behavior from multi-dimensional high-throughput batch-binding screen data. Kernel Ridge Regression is used to predict the first principal component for new molecular sequences. This workflow is demonstrated with a set of 97 monoclonal antibodies for five chromatography resins in two salt types across a range of pH and salt concentrations. Model development benchmarks four descriptor sets from biophysical structural models and protein language models. The investigation illustrates the value QSPR models can provide to purification process fit assessment, and selection of resins and operating conditions from sequence alone.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2439988"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950988","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

Correction.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/19420862.2025.2463770

引用次数: 0

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production. 通过工艺开发和gmp生产，对国内首创的抗癌IgE抗体药物MOv18进行理化和功能评价。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-01-20 DOI: 10.1080/19420862.2025.2451295

Heather J Bax, Jitesh Chauhan, Alexandra J McCraw, Melanie Grandits, Chara Stavraka, Heike Lentfer, Tim Hillyer, Simon Carroll, Kim Vigor, Chris Selkirk, Mariangela Figini, Jack Cheeseman, Paulina A Urbanowicz, Richard A Gardner, Daniel I R Spencer, Nigel Westwood, Sarah Mellor, James Spicer, Debra H Josephs, Sophia N Karagiannis

{"title":"Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production.","authors":"Heather J Bax, Jitesh Chauhan, Alexandra J McCraw, Melanie Grandits, Chara Stavraka, Heike Lentfer, Tim Hillyer, Simon Carroll, Kim Vigor, Chris Selkirk, Mariangela Figini, Jack Cheeseman, Paulina A Urbanowicz, Richard A Gardner, Daniel I R Spencer, Nigel Westwood, Sarah Mellor, James Spicer, Debra H Josephs, Sophia N Karagiannis","doi":"10.1080/19420862.2025.2451295","DOIUrl":"https://doi.org/10.1080/19420862.2025.2451295","url":null,"abstract":"Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards. During the process development and scaled Good Manufacturing Practice production, we demonstrate the retention of glycosylation state, biophysical profile, and functional characteristics of MOv18 IgE, including Fc-mediated mast cell degranulation and tumor cell killing. Assessment of manufacturing parameters shows expected pH, purity, concentration, and stability properties, as well as below threshold levels of known biological manufacturing contaminants. We confirm the suitability of the pipeline described for generating intact, functionally active, clinical-grade material for this novel therapeutic class as an Investigational Medicinal Product (IMP), with comparable characteristics to the original research-grade antibody. Furthermore, we screened patient blood ex vivo for potential type I hypersensitivity reaction to MOv18 IgE, using the basophil activation test, to identify patients not predicted to be hypersensitive to MOv18 IgE administration. This study supports the production of functionally active clinical grade (IMP) recombinant IgE and paves the way for the development of a new therapeutic antibody class for a range of antigenic specificities and disease settings.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2451295"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007982","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

Antibodies to watch in 2025. 抗体将在2025年问世。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2024-12-22 DOI: 10.1080/19420862.2024.2443538

Silvia Crescioli, Hélène Kaplon, Lin Wang, Jyothsna Visweswaraiah, Vaishali Kapoor, Janice M Reichert

{"title":"Antibodies to watch in 2025.","authors":"Silvia Crescioli, Hélène Kaplon, Lin Wang, Jyothsna Visweswaraiah, Vaishali Kapoor, Janice M Reichert","doi":"10.1080/19420862.2024.2443538","DOIUrl":"10.1080/19420862.2024.2443538","url":null,"abstract":"The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025. In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key trends in the development and approval of antibody formats such as bispecifics and ADCs, as well as clinical-phase transition and global approval success rates for these antibody formats, are reported.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2443538"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877593","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

Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments.

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-01 DOI: 10.1080/19420862.2025.2458627

Yun Hee Jeong, Gillian Lennon, Geertruida Veldman, Daniel M Serna, Alexander Ibrahimov

{"title":"Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments.","authors":"Yun Hee Jeong, Gillian Lennon, Geertruida Veldman, Daniel M Serna, Alexander Ibrahimov","doi":"10.1080/19420862.2025.2458627","DOIUrl":"10.1080/19420862.2025.2458627","url":null,"abstract":"Immunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance safety and efficacy of protein-based therapeutics. This study aimed to develop and validate a human in vitro immunogenicity T cell proliferation assay. However, there is a lack of comprehensive guidelines for managing product-related factors such as endotoxin contamination, which can significantly influence assay sensitivity and accuracy. Our investigation of the impact of endotoxins revealed that levels above 0.1 EU/mg significantly induce T cell proliferation and CD14+ myeloid cell expansion, leading to potential false-positive outcomes in immunogenicity assessments. These findings suggest the importance of developing standardized protocols to enhance the predictive capability of in vitro methods, ensuring the assessment of therapeutic proteins accurately reflects their immunogenic potential without interference from contaminants.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2458627"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074920","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

Sequence-based engineering of pH-sensitive antibodies for tumor targeting or endosomal recycling applications. 基于序列的 pH 值敏感抗体工程，用于肿瘤靶向或内体循环。

IF 5.3 2区医学

mAbs Pub Date : 2024-09-17 DOI: 10.1080/19420862.2024.2404064

Wanlei Wei,Traian Sulea

{"title":"Sequence-based engineering of pH-sensitive antibodies for tumor targeting or endosomal recycling applications.","authors":"Wanlei Wei,Traian Sulea","doi":"10.1080/19420862.2024.2404064","DOIUrl":"https://doi.org/10.1080/19420862.2024.2404064","url":null,"abstract":"The engineering of pH-sensitive therapeutic antibodies, particularly for improving effectiveness and specificity in acidic solid-tumor microenvironments, has recently gained traction. While there is a justified need for pH-dependent immunotherapies, current engineering techniques are tedious and laborious, requiring repeated rounds of experiments under different pH conditions. Inexpensive computational techniques to predict the effectiveness of His pH-switches require antibody-antigen complex structures, but these are lacking in most cases. To circumvent these requirements, we introduce a sequence-based in silico method for predicting His mutations in the variable region of antibodies, which could lead to pH-biased antigen binding. This method, called Sequence-based Identification of pH-sensitive Antibody Binding (SIpHAB), was trained on 3D-structure-based calculations of 3,490 antibody-antigen complexes with solved experimental structures. SIpHAB was parametrized to enhance preferential binding either toward or against the acidic pH, for selective targeting of solid tumors or for antigen release in the endosome, respectively. Applications to nine antibody-antigen systems with previously reported binding preferences at different pHs demonstrated the utility and enrichment capabilities of this high-throughput computational tool. SIpHAB, which only requires knowledge of the antibody primary amino-acid sequence, could enable a more efficient triage of pH-sensitive antibody candidates than could be achieved conventionally. An online webserver for running SipHAB is available freely at https://mm.nrc-cnrc.gc.ca/software/siphab/runner/.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"4 1","pages":"2404064"},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251356","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

Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors 对旨在减少与 Fc-gamma 受体结合的 Fc 突变的系统分析

IF 5.3 2区医学

mAbs Pub Date : 2024-09-15 DOI: 10.1080/19420862.2024.2402701

Geoff Hale, Jelle De Vos, Alastair Douglas Davy, Koen Sandra, Ian Wilkinson

引用次数: 0

Navigating large-volume subcutaneous injections of biopharmaceuticals: a systematic review of clinical pipelines and approved products 探索生物制药的大容量皮下注射：临床管线和已批准产品的系统回顾

IF 5.3 2区医学

mAbs Pub Date : 2024-09-15 DOI: 10.1080/19420862.2024.2402713

Philip Green, Andreas Schneider, Jakob Lange

引用次数: 0

Antibody association in solution: cluster distributions and mechanisms 溶液中的抗体关联：集群分布与机制

IF 5.3 2区医学

mAbs Pub Date : 2024-04-26 DOI: 10.1080/19420862.2024.2339582

Sandi Brudar, Leonid Breydo, Elisha Chung, Ken A. Dill, Nasim Ehterami, Ketan Phadnis, Samir Senapati, Mohammed Shameem, Xiaolin Tang, Muhammmad Tayyab, Barbara Hribar-Lee

引用次数: 0

Reducing neonatal Fc receptor binding enhances clearance and brain-to-blood ratio of TfR-delivered bispecific amyloid-β antibody 减少新生儿Fc受体结合可提高TfR递送的双特异性淀粉样蛋白-β抗体的清除率和脑血比

IF 5.3 2区医学

mAbs Pub Date : 2024-04-18 DOI: 10.1080/19420862.2024.2339337

Eva Schlein, Ken G. Andersson, Tiffany Dallas, Stina Syvänen, Dag Sehlin

引用次数: 0

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