mAbs最新文献 - Book学术

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":null,"pages":null},"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

Targeted CQA analytical control strategy for commercial antibody products: Replacing ion-exchange chromatography methods for charge heterogeneity with multi-attribute monitoring 针对商业抗体产品的 CQA 分析控制策略：用多属性监测取代电荷异质性离子交换色谱法

IF 5.3 2区医学

mAbs Pub Date : 2024-04-23 DOI: 10.1080/19420862.2024.2341641

Adam R Evans, Joseph Mulholland, Michael J Lewis, Ping Hu

{"title":"Targeted CQA analytical control strategy for commercial antibody products: Replacing ion-exchange chromatography methods for charge heterogeneity with multi-attribute monitoring","authors":"Adam R Evans, Joseph Mulholland, Michael J Lewis, Ping Hu","doi":"10.1080/19420862.2024.2341641","DOIUrl":"https://doi.org/10.1080/19420862.2024.2341641","url":null,"abstract":"ABSTRACT Peptide mapping with mass spectrometry (MS) is an important tool for protein characterization in the biopharmaceutical industry. Historically, peptide mapping monitors post-translational modifications (PTMs) of protein products and process intermediates during development. Multi-attribute monitoring (MAM) methods have been used previously in commercial release and stability testing panels to ensure control of selected critical quality attributes (CQAs). Our goal is to use MAM methods as part of an overall analytical testing strategy specifically focused on CQAs, while removing or replacing historical separation methods that do not effectively distinguish CQAs from non-CQAs due to co-elution. For example, in this study, we developed a strategy to replace a profile-based ion-exchange chromatography (IEC) method using a MAM method in combination with traditional purity methods to ensure control of charge variant CQAs for a commercial antibody (mAb) drug product (DP). To support this change in commercial testing strategy, the charge variant CQAs were identified and characterized during development by high-resolution LC-MS and LC-MS/MS. The charge variant CQAs included PTMs, high molecular weight species, and low molecular weight species. Thus, removal of the IEC method from the DP specification was achieved using a validated LC-MS MAM method on a QDa system to directly measure the charge variant PTM CQAs in combination with size exclusion chromatography (SE-HPLC) and capillary electrophoresis (CE-SDS) to measure the non-PTM charge variant CQAs. Bridging data between the MAM, IEC, and SE-HPLC methods were included in the commercial marketing application to justify removing IEC from the DP specification. We have also used this MAM method as a test for identity to reduce the number of QC assays. This strategy has received approvals from several health authorities.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140668832","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

Alternative splicing for tuneable expression of protein subunits at desired ratios 替代剪接可调整蛋白质亚基的表达比例

IF 5.3 2区医学

mAbs Pub Date : 2024-04-22 DOI: 10.1080/19420862.2024.2342243

Christel Aebischer-Gumy, Pierre Moretti, Timothee Brunstein Laplace, Jana Frank, Ysaline Grand, Farid Mosbaoui, Emilie Hily, Anna Galea, Megane Peltret, Carole Estoppey, Daniel Ayoub, Roberto Giovannini, Martin Bertschinger

{"title":"Alternative splicing for tuneable expression of protein subunits at desired ratios","authors":"Christel Aebischer-Gumy, Pierre Moretti, Timothee Brunstein Laplace, Jana Frank, Ysaline Grand, Farid Mosbaoui, Emilie Hily, Anna Galea, Megane Peltret, Carole Estoppey, Daniel Ayoub, Roberto Giovannini, Martin Bertschinger","doi":"10.1080/19420862.2024.2342243","DOIUrl":"https://doi.org/10.1080/19420862.2024.2342243","url":null,"abstract":"ABSTRACT The controlled expression of two or more proteins at a defined and stable ratio remains a substantial challenge, particularly in the bi- and multispecific antibody field. Achieving an optimal ratio of protein subunits can facilitate the assembly of multimeric proteins with high efficiency and minimize the production of by-products. In this study, we propose a solution based on alternative splicing, enabling the expression of a tunable and predefined ratio of two distinct polypeptide chains from the same pre-mRNA under the control of a single promoter. The pre-mRNA used in this study contains two open reading frames situated on separate exons. The first exon is flanked by two copies of the chicken troponin intron 4 (cTNT-I4) and is susceptible to excision from the pre-mRNA by means of alternative splicing. This specific design enables the modulation of the splice ratio by adjusting the strength of the splice acceptor. To illustrate this approach, we developed constructs expressing varying ratios of GFP and dsRED and extended their application to multimeric proteins such as monoclonal antibodies, achieving industrially relevant expression levels (>1 g/L) in a 14-day fed-batch process. The stability of the splice ratio was confirmed by droplet digital PCR in a stable pool cultivated over a 28-day period, while product quality was assessed via intact mass analysis, demonstrating absence of product-related impurities resulting from undesired splice events. Furthermore, we showcased the versatility of the construct by expressing two subunits of a bispecific antibody of the BEAT® type, which contains three distinct subunits in total.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140674050","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

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

Can antibodies be “vegan”? A guide through the maze of today’s antibody generation methods 抗体可以 "素食 "吗？穿越当今抗体生成方法迷宫的指南

IF 5.3 2区医学

mAbs Pub Date : 2024-04-18 DOI: 10.1080/19420862.2024.2343499

Stefan Dübel

引用次数: 0

Enrichment strategy and initial characterization of heterodimers enriched from a co-formulated cocktail of therapeutic antibodies against SARS-COV-2 从共同配制的抗SARS-COV-2治疗性抗体鸡尾酒中富集的异源二聚体的富集策略和初步特征描述

IF 5.3 2区医学

mAbs Pub Date : 2024-04-09 DOI: 10.1080/19420862.2024.2338301

Sophia Liu, Yuetian Yan, Cody M. Secor, Zachary R. Oberholtzer, Donna J. Skow, Mushhood Sheikh, Youmi Moon, Yue Fu, Cristinel Sandu, Shunhai Wang, Ning Li, Jennifer B. Nguyen, Michael P. Rosconi, Erica A. Pyles

引用次数: 0

Application of quantitative protein mass spectrometric data in the early predictive analysis of membrane-bound target engagement by monoclonal antibodies 定量蛋白质质谱数据在单克隆抗体膜结合目标参与早期预测分析中的应用

IF 5.3 2区医学

mAbs Pub Date : 2024-03-04 DOI: 10.1080/19420862.2024.2324485

Armin Sepp, Morris Muliaditan

引用次数: 0