IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-08-27 DOI: 10.1080/19420862.2024.2395503

Yutian Gan, Steffen Lippold, John Stobaugh, Christian Schöneich, Feng Yang

{"title":"Expanding the structural resolution of glycosylation microheterogeneity in therapeutic proteins by salt-free hydrophilic interaction liquid chromatography tandem mass spectrometry.","authors":"Yutian Gan, Steffen Lippold, John Stobaugh, Christian Schöneich, Feng Yang","doi":"10.1080/19420862.2024.2395503","DOIUrl":"10.1080/19420862.2024.2395503","url":null,"abstract":"Glycosylation affects the safety and efficacy of therapeutic proteins and is often considered a critical quality attribute (CQA). Therefore, it is important to identify and quantify glycans during drug development. Glycosylation is a highly complex post-translational modification (PTM) due to its structural heterogeneity, i.e. glycosylation site occupancy, glycan compositions, modifications, and isomers. Current analytical tools compromise either structural resolution or site specificity. Hydrophilic interaction liquid chromatography-fluorescence-mass spectrometry (HILIC-FLR-MS) is the gold standard for structural analysis of released glycans, but lacks information on site specificity and occupation. However, HILIC-FLR-MS often uses salt in the solvent, which impairs analysis robustness and sensitivity. Site-specific glycosylation analysis via glycopeptides, upon proteolytic digestion, is commonly performed by reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS), but provides only compositional and limited structural glycan information. In this study, we introduce a salt-free, glycopeptide-based HILIC-tandem mass spectrometry (HILIC-MS/MS) method that provides glycan identification, glycan isomer separation and site-specific information simultaneously. Moreover, HILIC-MS/MS demonstrated comparable relative quantification results as released glycan HILIC-FLR-MS. Further, our new method improves the retention of hydrophilic peptides, allowing simultaneous analysis of important CQAs such as deamidation in antibodies. The developed method offers a valuable tool to streamline the site-specific glycosylation analysis of glycoproteins, which is particularly important for the expanding landscape of novel therapeutic formats in the biopharmaceutical industry.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2395503"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080727","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

Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood-brain barrier and interacts with amyloid β. 靶向淀粉样蛋白β和TfR的单域抗体-scFv共轭物可穿透血脑屏障并与淀粉样蛋白β相互作用。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-10-02 DOI: 10.1080/19420862.2024.2410968

Rebecca Faresjö, Elisabet O Sjöström, Tiffany Dallas, Magnus M Berglund, Jonas Eriksson, Dag Sehlin, Stina Syvänen

{"title":"Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood-brain barrier and interacts with amyloid β.","authors":"Rebecca Faresjö, Elisabet O Sjöström, Tiffany Dallas, Magnus M Berglund, Jonas Eriksson, Dag Sehlin, Stina Syvänen","doi":"10.1080/19420862.2024.2410968","DOIUrl":"10.1080/19420862.2024.2410968","url":null,"abstract":"Neurodegenerative diseases such as Alzheimer's disease (AD) pose substantial challenges to patients and health-care systems, particularly in countries with aging populations. Immunotherapies, including the marketed antibodies lecanemab (Leqembi®) and donanemab (KisunlaTM), offer promise but face hurdles due to limited delivery across the blood-brain barrier (BBB). This limitation necessitates high doses, resulting in increased costs and a higher risk of side effects. This study explores transferrin receptor (TfR)-binding camelid single-domain antibodies (VHHs) for facilitated brain delivery. We developed and evaluated fusion proteins (FPs) combining VHHs with human IgG Fc domains or single-chain variable fragments (scFvs) of the anti-amyloid-beta (Aβ) antibody 3D6. In vitro assessments showed varying affinities of the FPs for TfR. In vivo evaluations indicated that specific VHH-Fc and VHH-scFv fusions reached significant brain concentrations, emphasizing the importance of optimal TfR binding affinities. The VHH-scFv fusions were further investigated in mouse models with Aβ pathology, showing higher retention compared to wild-type mice without Aβ pathology. Our findings suggest that these novel VHH-based FPs hold potential for therapeutic and diagnostic applications in AD, providing a strategy to overcome BBB limitations and enhance brain targeting of antibody-based treatments. Furthermore, our results suggest that a given bispecific TfR-binding fusion format has a window of \"optimal\" affinity where parenchymal delivery is adequate, while blood pharmacokinetics aligns with the desired application of the fusion protein.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2410968"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365771","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

Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation. 不同 cIEF 系统治疗性单克隆抗体的电荷异质性：对当前形势的看法。

IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-02-08 DOI: 10.1080/19420862.2024.2313737

Alessandro Ascione, Marcello Belfiore, Jaana Vesterinen, Mihaela Buda, Wolf Holtkamp, Francesca Luciani

{"title":"Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation.","authors":"Alessandro Ascione, Marcello Belfiore, Jaana Vesterinen, Mihaela Buda, Wolf Holtkamp, Francesca Luciani","doi":"10.1080/19420862.2024.2313737","DOIUrl":"10.1080/19420862.2024.2313737","url":null,"abstract":"Therapeutic mAbs show a specific \"charge fingerprint\" that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusing (cIEF), commonly used for the evaluation of such CQA, provides an analytical tool to investigate mAb purity and identity across the product lifecycle. Here, we discuss the results of an analysis of a panel of antibody products by conventional and whole-column imaging cIEF systems performed as part of European Pharmacopoeia activities related to development of \"horizontal standards\" for the quality control of monoclonal antibodies (mAbs). The study aimed at designing and verifying an independent and transversal cIEF procedure for the reliable analysis of mAbs charge variants. Despite the use of comparable experimental conditions, discrepancies in the charge profile and measured isoelectric points emerged between the two cIEF systems. These data suggest that the results are method-dependent rather than absolute, an aspect known to experts in the field and pharmaceutical industry, but not suitably documented in the literature. Critical implications from analytical and regulatory perspectives, are herein thoughtfully discussed, with a special focus on the context of market surveillance and identification of falsified medicines.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2313737"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707134","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

Applications and challenges in designing VHH-based bispecific antibodies: leveraging machine learning solutions. 设计基于 VHH 的双特异性抗体的应用与挑战：利用机器学习解决方案。

IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-04-26 DOI: 10.1080/19420862.2024.2341443

Michael Mullin, James McClory, Winston Haynes, Justin Grace, Nathan Robertson, Gino van Heeke

{"title":"Applications and challenges in designing VHH-based bispecific antibodies: leveraging machine learning solutions.","authors":"Michael Mullin, James McClory, Winston Haynes, Justin Grace, Nathan Robertson, Gino van Heeke","doi":"10.1080/19420862.2024.2341443","DOIUrl":"https://doi.org/10.1080/19420862.2024.2341443","url":null,"abstract":"The development of bispecific antibodies that bind at least two different targets relies on bringing together multiple binding domains with different binding properties and biophysical characteristics to produce a drug-like therapeutic. These building blocks play an important role in the overall quality of the molecule and can influence many important aspects from potency and specificity to stability and half-life. Single-domain antibodies, particularly camelid-derived variable heavy domain of heavy chain (VHH) antibodies, are becoming an increasingly popular choice for bispecific construction due to their single-domain modularity, favorable biophysical properties, and potential to work in multiple antibody formats. Here, we review the use of VHH domains as building blocks in the construction of multispecific antibodies and the challenges in creating optimized molecules. In addition to exploring traditional approaches to VHH development, we review the integration of machine learning techniques at various stages of the process. Specifically, the utilization of machine learning for structural prediction, lead identification, lead optimization, and humanization of VHH antibodies.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2341443"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867231","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. 更正。

IF 5.3 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-06-07 DOI: 10.1080/19420862.2024.2364972

引用次数: 0

Identification of novel anti-CD16a antibody clones for the development of effective natural killer cell engagers. 鉴定新型抗 CD16a 抗体克隆，以开发有效的自然杀伤细胞吸引器。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-07-24 DOI: 10.1080/19420862.2024.2381261

Bill Liao, Christine Tumanut, Lin Li, Adam Corper, Dilip Challa, Alex Chang, Hydari Begum, Elinaz Farokhi, Catherine Woods, Xiaomin Fan

{"title":"Identification of novel anti-CD16a antibody clones for the development of effective natural killer cell engagers.","authors":"Bill Liao, Christine Tumanut, Lin Li, Adam Corper, Dilip Challa, Alex Chang, Hydari Begum, Elinaz Farokhi, Catherine Woods, Xiaomin Fan","doi":"10.1080/19420862.2024.2381261","DOIUrl":"10.1080/19420862.2024.2381261","url":null,"abstract":"Natural killer (NK) cells are key players in human innate immunity. Cell engager antibody formats that recruit and activate NK cells more effectively have emerged as a promising immunotherapy approach to target cancer cells through more effective antibody-dependent cell-mediated cytotoxicity (ADCC). Monoclonal antibody drugs with ADCC activity have shown clinical benefit and improved outcomes for patients with certain types of cancer. CD16a, a Fc gamma III receptor, is the major component that is responsible for the ADCC activity of NK cells. Screening AvantGen's yeast displayed human antibody libraries led to the isolation of 2 antibody clones, #1A2 and #2-2A2, that selectively recognize both isoforms (F and V) of CD16a on primary NK cells with high affinity, yet minimally (#1A2) or do not (#2-2A2) cross-react with both allelotypes of CD16b (NA1 and NA2) expressed by neutrophils. Epitope mapping studies revealed that they bind to an epitope dependent on residue Y158 of CD16a, since mutation of Y158 to the corresponding CD16b residue H158 completely abolishes binding to CD16a. When formatted as bispecific antibodies targeting CD16a and a tumor-associated antigen (TAA, e.g. CD19), they exhibit specific binding to NK cells and induce potent NK cell activation upon encountering tumor cells, resulting in effective tumor cell killing. Notably, these bispecific antibody engagers stimulate NK cell cytokine release during co-culture with target cells, resulting in target cell cytotoxicity. These anti-CD16a antibody clones are promising candidates for combination with any TAA of interest, offering the potential for novel NK cell engager-based cancer therapeutics that are minimally affected by the high concentrations of human IgG in the circulation.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2381261"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759613","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

A comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs. 对全长抗体、片段抗体和双特异性抗体的可开发性进行比较研究后发现，工程构建物的稳定性风险更高。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-10-04 DOI: 10.1080/19420862.2024.2403156

Itzel Condado-Morales, Fabian Dingfelder, Isabel Waibel, Oliver M Turnbull, Bhargav Patel, Zheng Cao, Jais Rose Bjelke, Susanne Nedergaard Grell, Anja Bennet, Alissa M Hummer, Matthew I J Raybould, Charlotte M Deane, Thomas Egebjerg, Nikolai Lorenzen, Paolo Arosio

{"title":"A comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs.","authors":"Itzel Condado-Morales, Fabian Dingfelder, Isabel Waibel, Oliver M Turnbull, Bhargav Patel, Zheng Cao, Jais Rose Bjelke, Susanne Nedergaard Grell, Anja Bennet, Alissa M Hummer, Matthew I J Raybould, Charlotte M Deane, Thomas Egebjerg, Nikolai Lorenzen, Paolo Arosio","doi":"10.1080/19420862.2024.2403156","DOIUrl":"10.1080/19420862.2024.2403156","url":null,"abstract":"Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics. We measured 15 biophysical properties related to activity, manufacturing, and stability, scoring variants with a flag-based risk approach and a recent in silico developability profiler. Our comparative assessment revealed that overall developability is higher for the natural full-length antibody format. Bispecific antibodies, antibodies with scFv fragments at the C-terminus of the light chain, and single-chain Fv antibody fragments (scFvs) have intermediate developability properties, while more complicated formats, such as scFv- scFv, bispecific mAbs with one Fab exchanged with a scFv, and diabody formats are collectively more challenging. In particular, our study highlights the propensity for fragmentation and aggregation, both in bulk and at interfaces, for many current engineered formats.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2403156"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372151","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

Anti-HER2 biparatopic antibody KJ015 has near-native structure, functional balanced high affinity, and synergistic efficacy with anti-PD-1 treatment in vivo. 抗 HER2 双抗体 KJ015 具有接近原生的结构、功能平衡的高亲和力以及与体内抗 PD-1 治疗的协同效应。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-10-09 DOI: 10.1080/19420862.2024.2412881

Zheng Wang, Yu Liu, Yunxia Xu, Lin Lu, Zhen Zhu, Baojie Lv, Xin Fang, Yao Tang, Jinhua Wang, Yu Cheng, Ying Hu, Junwen Lou, Peican Wu, Chendan Liu, Yanjun Liu, Xin Zeng, Qing Xu

{"title":"Anti-HER2 biparatopic antibody KJ015 has near-native structure, functional balanced high affinity, and synergistic efficacy with anti-PD-1 treatment in vivo.","authors":"Zheng Wang, Yu Liu, Yunxia Xu, Lin Lu, Zhen Zhu, Baojie Lv, Xin Fang, Yao Tang, Jinhua Wang, Yu Cheng, Ying Hu, Junwen Lou, Peican Wu, Chendan Liu, Yanjun Liu, Xin Zeng, Qing Xu","doi":"10.1080/19420862.2024.2412881","DOIUrl":"10.1080/19420862.2024.2412881","url":null,"abstract":"Currently approved human epidermal growth factor receptor 2 (HER2)-targeted antibody therapies are largely derived from trastuzumab, including trastuzumab-chemotherapy combinations, fixed-dose trastuzumab-pertuzumab combinations, and trastuzumab antibody-drug conjugates. To expand the options, bispecific antibodies, which may better utilize the benefits of combination therapy, are being developed. Among them, biparatopic antibodies (bpAbs) have shown improved efficacy compared to monoclonal antibody (mAb) combinations in HER2-positive patients. BpAbs bind two independent epitopes on the same antigen, which allows fine-tuning of mechanisms of action, including enhancement of on-target specificity and induction of strong antigen clustering due to the unique binding mode. To fully utilize the potential of bpAbs for anti-HER2 drug development, it is crucial to consider formats that offer stability and high-yield production, along with a functional balance between the two epitopes. In this study, we rationally designed a bpAb, KJ015, that shares a common light chain with two Fab arms and exhibits functionally balanced high affinity for two HER2 non-overlapping epitopes. KJ015 demonstrated high-expression titers over 7 g/L and stable physicochemical properties at elevated concentrations, facilitating subcutaneous administration with hyaluronidase. Moreover, KJ015 maintained comparable antibody-dependent cytotoxicity, phagocytosis, and complement-dependent cytotoxicity with trastuzumab plus pertuzumab. It exhibited enhanced synergy when administered subcutaneously with hyaluronidase and anti-PD-1 mAb in a mouse tumor model, suggesting promising clinical prospects for this combination.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2412881"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391661","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

Development of a novel, high-throughput imaged capillary isoelectric focusing-Western method to characterize charge heterogeneity of monoclonal antibody heavy and light chains. 开发一种新型、高通量成像毛细管等电聚焦--西方法，用于表征单克隆抗体重链和轻链的电荷异质性。

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-11-15 DOI: 10.1080/19420862.2024.2429414

Gangadhar Dhulipala, Alanna Broszeit, Kun Lu, Nisha Palackal, Erica Pyles

{"title":"Development of a novel, high-throughput imaged capillary isoelectric focusing-Western method to characterize charge heterogeneity of monoclonal antibody heavy and light chains.","authors":"Gangadhar Dhulipala, Alanna Broszeit, Kun Lu, Nisha Palackal, Erica Pyles","doi":"10.1080/19420862.2024.2429414","DOIUrl":"10.1080/19420862.2024.2429414","url":null,"abstract":"Charge heterogeneity is one of the commonly monitored quality attributes in biotherapeutics. It can impact the stability, efficacy, and safety of products, but it can also affect the pharmacokinetics, binding affinity, and overall biological activity of the molecules. Given the substantial size and complexity of antibodies, subtle variations or specific modifications that result in charge heterogeneity might be concealed when mAbs are analyzed under native conditions. Two-dimensional gel electrophoresis has traditionally been used to characterize antibody heavy chain (HC) and light chain (LC) charge variants. The procedures, however, are laborious, and the method is only qualitative. ChromiCE was developed as an alternative approach to provide quantitative analysis, but the method is also labor intensive, requiring separation of the HC and LC by chromatography before imaged capillary isoelectric focusing (iCIEF) analysis. We thus developed a novel, automated high-throughput iCIEF-Western method to directly quantify the HC and LC charge variants with high sensitivity under denatured and reduced conditions. The HC and LC charge variants are selectively characterized using detection antibodies specific to the HC or LC. In addition, the reduced, denatured iCIEF-Western method allows for the analysis of up to 96 samples overnight, offering good precision and high throughput with minimal analyst hands-on time. Further, the developed method can be applied in different aspects of drug development, such as comparability, release or stability testing given its ability to provide identity, as well as qualitative and quantitative comparative analysis.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2429414"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639260","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 2024. 2024 年值得关注的抗体

IF 5.6 2区医学

mAbs Pub Date : 2024-01-01 Epub Date: 2024-01-05 DOI: 10.1080/19420862.2023.2297450

Silvia Crescioli, Hélène Kaplon, Alicia Chenoweth, Lin Wang, Jyothsna Visweswaraiah, Janice M Reichert

{"title":"Antibodies to watch in 2024.","authors":"Silvia Crescioli, Hélène Kaplon, Alicia Chenoweth, Lin Wang, Jyothsna Visweswaraiah, Janice M Reichert","doi":"10.1080/19420862.2023.2297450","DOIUrl":"10.1080/19420862.2023.2297450","url":null,"abstract":"The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2297450"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098161","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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