IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-07-10 DOI: 10.1080/19420862.2025.2531223

Cristina Bergamaschi, Miguel Gaspar, Thomas Ciucci, Suzanne I Sitnikova, Corinne Cayatte, Mike Pica, Simon J Dovedi

{"title":"Innovative strategies for T cell engagers for cancer immunotherapy.","authors":"Cristina Bergamaschi, Miguel Gaspar, Thomas Ciucci, Suzanne I Sitnikova, Corinne Cayatte, Mike Pica, Simon J Dovedi","doi":"10.1080/19420862.2025.2531223","DOIUrl":"10.1080/19420862.2025.2531223","url":null,"abstract":"T cell engagers (TCEs) are a promising class of cancer immunotherapy that re-direct T cells to kill tumor cells. However, their clinical application is limited by several challenges, including cytokine release syndrome (CRS), on-target off-tumor toxicity and overcoming immunosuppression in both hematological and solid tumors. This review explores recent innovations in TCE design aimed at improving their safety and efficacy. Key developments include optimizing geometry to facilitate effective immune synapses, affinity optimization of the anti-CD3/TCR domain and targeting of specific T cell subsets which both aim to reduce CRS. Logic-gated approaches such as dual-targeted and conditional TCEs activated by tumor microenvironment factors have the potential to reduce on target, off tumor toxicity and potentially increase the depth and durability of response. Additionally, leveraging costimulatory signaling offers the potential to further improve efficacy across hematological and solid tumor settings. The next generation of TCEs is expected to overcome some of the limitations of conventional TCEs, enhancing their therapeutic window and enabling combination therapies. As the field advances, TCEs are poised to become a cornerstone of cancer immunotherapy, potentially improving outcomes for a broader range of patients than the ones currently benefiting from conventional immunotherapy.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2531223"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608728","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

NMR-based structural integrity analysis of therapeutic monoclonal antibodies: a comparative study of Humira and its biosimilars. 基于核磁共振的治疗性单克隆抗体结构完整性分析：Humira及其生物仿制药的比较研究。

IF 7.3 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI: 10.1080/19420862.2025.2551208

Donna Baldisseri, Shen Luo, Christelle Anne F Ancajas, Uriel Ortega-Rodriguez, Christian Fischer, Guozhang Zou, Jianghong Gu, David Keire, Martial Piotto, Baolin Zhang

{"title":"NMR-based structural integrity analysis of therapeutic monoclonal antibodies: a comparative study of Humira and its biosimilars.","authors":"Donna Baldisseri, Shen Luo, Christelle Anne F Ancajas, Uriel Ortega-Rodriguez, Christian Fischer, Guozhang Zou, Jianghong Gu, David Keire, Martial Piotto, Baolin Zhang","doi":"10.1080/19420862.2025.2551208","DOIUrl":"10.1080/19420862.2025.2551208","url":null,"abstract":"The analytical comparability of biologic products and their biosimilars, including higher-order structure (HOS) assessment, ensures product quality and is required for regulatory approval. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to evaluate the HOS of Humira (adalimumab) and its biosimilars under normal and photo-stressed conditions. Under normal conditions, 1D and 2D NMR spectra showed strong structural similarity among all products. However, photo-stressed samples exhibited distinct structural differences, including increased methionine oxidation, and localized conformational changes, most notably in the reference product. These changes correlated with findings from size-exclusion chromatography, capillary isoelectric focusing, and mass spectrometry (MS), which revealed size and charge heterogeneity, as well as site-specific methionine oxidation in the heavy chains. The differences in photostability were found to be influenced by container closure systems (CCSs) and formulations. In contrast, circular dichroism spectral analysis showed minimal variation in secondary structures among stressed and unstressed samples. These results underscore the utility of NMR as a sensitive tool for comparative structural analysis of monoclonal antibodies and their biosimilars, particularly under stress conditions, and highlight the impact of formulation and CCS on product stability.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2551208"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023676","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

Predicting purification process fit of monoclonal antibodies using machine learning. 利用机器学习预测单克隆抗体的纯化工艺拟合。

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

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

Homogeneous antibody-drug conjugates with dual payloads: potential, methods and considerations. 具有双重有效载荷的均质抗体-药物偶联物：潜力、方法和考虑。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-05-05 DOI: 10.1080/19420862.2025.2498162

Miao Wen, Abigail Yu, Young Park, Daniel Calarese, Hans-Peter Gerber, Gang Yin

{"title":"Homogeneous antibody-drug conjugates with dual payloads: potential, methods and considerations.","authors":"Miao Wen, Abigail Yu, Young Park, Daniel Calarese, Hans-Peter Gerber, Gang Yin","doi":"10.1080/19420862.2025.2498162","DOIUrl":"https://doi.org/10.1080/19420862.2025.2498162","url":null,"abstract":"The development of site-specific dual-payload antibody-drug conjugates (ADCs) represents a potential advancement in targeted cancer therapy, enabling the simultaneous delivery of two distinct drugs into the same cancer cells to overcome payload resistance and enhance therapeutic efficacy. Here, we examine various methodologies for achieving site-specific dual-payload conjugation, including the use of multi-functional linkers, canonical amino acids, non-canonical amino acids, and enzyme-mediated methods, all of which facilitate precise control over payload attachment while ensuring homogeneity. We explore the implications of different conjugation techniques on drug-to-antibody ratios and the ratios of the two payloads, as well as their impact on process complexity and manufacturability. Additionally, we address the potential advantages of dual-payload ADCs compared to ADCs combined with traditional chemotherapy or single-payload ADC/ADC combinations. By evaluating these innovative methods, we aim to provide a comprehensive understanding of the current landscape in dual-payload ADC development and outline emerging directions necessary for further advancement of this promising therapeutic strategy.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2498162"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006950","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

How to think about designing smart antibodies in the age of genAI: integrating biology, technology, and experience. 如何思考在基因ai时代设计智能抗体：整合生物学、技术和经验。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-04-10 DOI: 10.1080/19420862.2025.2490790

Andrew Buchanan, Eric Bennett, Rebecca Croasdale-Wood, Andreas Evers, Brian Fennell, Norbert Furtmann, Konrad Krawczyk, Sandeep Kumar, Christopher James Langmead, Melody Shahsavarian, Christine Elaine Tinberg

引用次数: 0

Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments. 建立内毒素限度以提高体外免疫原性风险评估的可靠性。

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

Achieving Acceleration to First-in-Human: MSD's Learnings on Platform Method Validation Strategy. 加速实现首次人体试验：MSD在平台方法验证策略上的学习。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-18 DOI: 10.1080/19420862.2025.2468840

Xiaoqing Hua, Jorge Quiroz, Joop Waterval, Brian Harrison, Maria DeBruin, Lynn Gennaro

{"title":"Achieving Acceleration to First-in-Human: MSD's Learnings on Platform Method Validation Strategy.","authors":"Xiaoqing Hua, Jorge Quiroz, Joop Waterval, Brian Harrison, Maria DeBruin, Lynn Gennaro","doi":"10.1080/19420862.2025.2468840","DOIUrl":"10.1080/19420862.2025.2468840","url":null,"abstract":"Over the past decades, the number of therapeutic protein pipelines in early-phase clinical studies has increased dramatically. The rapid growth in the pipeline underscores the need to accelerate early-stage development and enable fast first-in-human (FIH) trials to bring novel therapies to patients. Across the industry, various efforts have been developed to achieve this goal. In this communication, a platform analytical method validation approach developed and used by MSD for FIH programs is described. A case study from the release panel, a polysorbate 80 (PS-80) platform method is utilized to illustrate the workflow. In this approach, historical validation data within the same modality are summarized and supplemented with statistical analyses to justify a limited validation for future pipeline projects. The platform method validation strategy has reduced the overall validation timeline from up to 4 months to 1-2 months and has successfully been implemented in FIH filings. This communication provides insights to pharmaceutical companies interested in developing platform analytical method validation approaches for fast FIH studies.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2468840"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449153","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

Quantifying antibody binding: techniques and therapeutic implications. 定量抗体结合：技术和治疗意义。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-16 DOI: 10.1080/19420862.2025.2459795

James Lodge, Lewis Kajtar, Rachel Duxbury, David Hall, Glenn A Burley, Joanna Cordy, James W T Yates, Zahra Rattray

引用次数: 0

Optimizing asymmetric antibody purification: a semi-automated process and its digital integration. 优化非对称抗体纯化：半自动化过程及其数字化集成。

IF 5.6 2区医学

mAbs Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/19420862.2025.2467388

Christophe Prince, Despoina Georgiadou, Manuela Machatti, Matthias Hermann, Erwin van Puijenbroek

{"title":"Optimizing asymmetric antibody purification: a semi-automated process and its digital integration.","authors":"Christophe Prince, Despoina Georgiadou, Manuela Machatti, Matthias Hermann, Erwin van Puijenbroek","doi":"10.1080/19420862.2025.2467388","DOIUrl":"10.1080/19420862.2025.2467388","url":null,"abstract":"Over the past decades, immunization and display technologies have considerably increased the potential for generating new binders against cell surface targets. Concomitantly, the complexity of biologic therapeutic drugs has also increased, with new asymmetric formats such as bispecific antibodies or antibody fusion proteins making the supply of molecules for preclinical drug discovery more challenging. The purification of those molecules is crucial, and an efficient purification platform for drug discovery research units should have multiple aims. First, it needs to deliver the highest quality proteins for research activities at a fast pace in order to increase screening capacities. Second, it has to deliver protein with sufficient yield in order to cover the project requirements and minimize the repetition of production cycles. Through a case study for a bispecific antibody, we describe a semi-automated and digitalized purification platform aiming at accelerating and optimizing the supply of asymmetric antibodies for drug discovery. We show how the automation of repetitive tasks and the digitalization of the process can lead to increased throughput in the context of complex purifications, including a cation exchange chromatography separation step. Furthermore, we highlight how process digitalization leads to enhanced data capture and accessibility, facilitating decision-making along the purification process. With a maximal throughput of 36 asymmetric antibodies per week and data proving the consistency of the quality delivered, this platform represents a step forward in the supply of complex antibody formats for preclinical drug discovery.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2467388"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542511","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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