mAbs最新文献

{"title":"Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy.","authors":"Amelia C McCue, Stephen J Demarest, Karen J Froning, Michael J Hickey, Stephen Antonysamy, Brian Kuhlman","doi":"10.1080/19420862.2024.2373325","DOIUrl":"10.1080/19420862.2024.2373325","url":null,"abstract":"<p><p>T-cell engaging (TCE) bispecific antibodies are potent drugs that trigger the immune system to eliminate cancer cells, but administration can be accompanied by toxic side effects that limit dosing. TCEs function by binding to cell surface receptors on T cells, frequently CD3, with one arm of the bispecific antibody while the other arm binds to cell surface antigens on cancer cells. On-target, off-tumor toxicity can arise when the target antigen is also present on healthy cells. The toxicity of TCEs may be ameliorated through the use of pro-drug forms of the TCE, which are not fully functional until recruited to the tumor microenvironment. This can be accomplished by masking the anti-CD3 arm of the TCE with an autoinhibitory motif that is released by tumor-enriched proteases. Here, we solve the crystal structure of the antigen-binding fragment of a novel anti-CD3 antibody, E10, in complex with its epitope from CD3 and use this information to engineer a masked form of the antibody that can activate by the tumor-enriched protease matrix metalloproteinase 2 (MMP-2). We demonstrate with binding experiments and <i>in vitro</i> T-cell activation and killing assays that our designed prodrug TCE is capable of tumor-selective T-cell activity that is dependent upon MMP-2. Furthermore, we demonstrate that a similar masking strategy can be used to create a pro-drug form of the frequently used anti-CD3 antibody SP34. This study showcases an approach to developing immune-modulating therapeutics that prioritizes safety and has the potential to advance cancer immunotherapy treatment strategies.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2373325"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498394","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}

{"title":"FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques.","authors":"Joanna Zikos, Gabriela M Webb, Helen L Wu, Jason S Reed, Jennifer Watanabe, Jodie L Usachenko, Ala M Shaqra, Celia A Schiffer, Koen K A Van Rompay, Jonah B Sacha, Diogo M Magnani","doi":"10.1080/19420862.2024.2406788","DOIUrl":"10.1080/19420862.2024.2406788","url":null,"abstract":"<p><p>Prenatal administration of monoclonal antibodies (mAbs) is a strategy that could be exploited to prevent viral infections during pregnancy and early life. To reach protective levels in fetuses, mAbs must be transported across the placenta, a selective barrier that actively and specifically promotes the transfer of antibodies (Abs) into the fetus through the neonatal Fc receptor (FcRn). Because FcRn also regulates Ab half-life, Fc mutations like the M428L/N434S, commonly known as LS mutations, and others have been developed to enhance binding affinity to FcRn and improve drug pharmacokinetics. We hypothesized that these FcRn-enhancing mutations could similarly affect the delivery of therapeutic Abs to the fetus. To test this hypothesis, we measured the transplacental transfer of leronlimab, an anti-CCR5 mAb, in clinical development for preventing HIV infections, using pregnant rhesus macaques to model <i>in utero</i> mAb transfer. We also generated a stabilized and FcRn-enhanced form of leronlimab, termed leronlimab-PLS. Leronlimab-PLS maintained higher levels within the maternal compartment while also reaching higher mAb levels in the fetus and newborn circulation. Further, a single dose of leronlimab-PLS led to complete CCR5 receptor occupancy in mothers and newborns for almost a month after birth. These findings support the optimization of FcRn interactions in mAb therapies designed for administration during pregnancy.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2406788"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349520","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}

{"title":"Rapid depletion of \"catch-and-release\" anti-ASGR1 antibody in vivo.","authors":"Siva Charan Devanaboyina, Peng Li, Edward L LaGory, Carrie Poon-Andersen, Kevin D Cook, Marcus Soto, Zhe Wang, Khue Dang, Craig Uyeda, Ryan B Case, Veena A Thomas, Ronya Primack, Manuel Ponce, Mei Di, Brian Ouyang, Joelle Kaner, Sheung Kwan Lam, Mina Mostafavi","doi":"10.1080/19420862.2024.2383013","DOIUrl":"10.1080/19420862.2024.2383013","url":null,"abstract":"<p><p>Targeting antigens with antibodies exhibiting pH/Ca²⁺-dependent binding against an antigen is an attractive strategy to mitigate target-mediated disposition and antigen buffering. Studies have reported improved serum exposure of antibodies exhibiting pH/Ca²⁺-binding against membrane-bound receptors. Asialoglycoprotein receptor 1 (ASGR1) is a membrane-bound receptor primarily localized in hepatocytes. With a high expression level of approximately one million receptors per cell, high turnover, and rapid recycling, targeting this receptor with a conventional antibody is a challenge. In this study, we identified an antibody exhibiting pH/Ca²⁺-dependent binding to ASGR1 and generated antibody variants with increased binding to neonatal crystallizable fragment receptor (FcRn). Serum exposures of the generated anti-ASGR1 antibodies were analyzed in transgenic mice expressing human FcRn. Contrary to published reports of increased serum exposure of pH/Ca²⁺-dependent antibodies, the pH/Ca²⁺-dependent anti-ASGR1 antibody had rapid serum clearance in comparison to a conventional anti-ASGR1 antibody. We conducted sub-cellular trafficking studies of the anti-ASGR1 antibodies along with receptor quantification analysis for mechanistic understanding of the rapid serum clearance of pH/Ca²⁺-dependent anti-ASGR1 antibody. The findings from our study provide valuable insights in identifying the antigens, especially membrane bound, that may benefit from targeting with pH/Ca²⁺-dependent antibodies to obtain increased serum exposure.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2383013"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759614","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}

{"title":"GB18-06, a nanobody targeting GDF15, effectively alleviates weight loss and restores physical function in cachexia models.","authors":"Yu Huang, Jinyong Wang, Xiling Wei, Hui Zhang, Wei Shang, Xiangling Zhang, Lanjiao Zhai, Xi Chen, Huiming Li, Suofu Qin","doi":"10.1080/19420862.2024.2416453","DOIUrl":"10.1080/19420862.2024.2416453","url":null,"abstract":"<p><p>Cachexia is a complicated metabolic syndrome mainly associated with cancers, characterized by extreme weight loss and muscle wasting. It is a debilitating condition that negatively affects prognosis and survival. However, there is currently no effective pharmacological intervention that can reverse body weight loss and improve physical performance in patients with cachexia. Growth differentiation factor 15 (GDF15) can suppress appetite and regulate energy balance through binding to glial cell-derived neurotrophic factor receptor alpha-like (GFRAL). In order to develop a novel, effective treatment for cachexia, we generated a GDF15-targeting VHH nanobody, GB18-06, that was able to bind GDF15 with high affinity. <i>In vitro</i>, GB18-06 potently inhibited the GDF15-GFRAL signaling pathway, leading to a reduction of downstream ERK and AKT phosphorylation levels; <i>in vivo</i>, GB18-06 alleviated weight loss (>20%) in cancer and chemotherapy-induced cachexia models in mice. Compared with the control (phosphate-buffered saline) group, the ambulatory activity of mice in the GB18-06-treated group also increased 77%. Furthermore, GB18-06 exhibited desirable pharmacokinetic properties and an excellent developability profile. Our study has demonstrated a means of developing targeted treatment for cachexia with high efficacy, potentially leading to improved clinical outcomes and quality of life for patients with cachexia.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2416453"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469143","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}

{"title":"Residue-resolved insights into the stabilization of therapeutic proteins by excipients: A case study of two monoclonal antibodies with arginine and glutamate.","authors":"Tobias M Prass, Patrick Garidel, Lars V Schäfer, Michaela Blech","doi":"10.1080/19420862.2024.2427771","DOIUrl":"10.1080/19420862.2024.2427771","url":null,"abstract":"<p><p>Protein formulation development relies on the selection of excipients that inhibit protein-protein interactions preventing aggregation. Empirical strategies involve screening many excipient and buffer combinations by physicochemical characterization using forced degradation or temperature-induced stress, mostly under accelerated conditions. Such methods do not readily provide information on the inter- and intramolecular interactions responsible for the effects of excipients. Here, we describe a combined experimental and computational approach for investigating the effect of protein-excipient interactions on formulation stability, which allows the identification of preferential interaction sites and thus can aid in the selection of excipients to be experimentally screened. Model systems composed of two marketed therapeutic IgG1 monoclonal antibodies with identical Fc domain sequences, trastuzumab and omalizumab, were investigated with commonly used excipients arginine, glutamate, and equimolar arginine/glutamate mixtures. Protein-excipient interactions were studied using all-atom molecular dynamics (MD) simulations, which show accumulation of the excipients at specific antibody regions. Preferential excipient-interaction sites were particularly found for charged and aromatic residues and in the complementary-determining regions, with more pronounced arginine contacts for omalizumab than trastuzumab. These computational findings are in line with the more pronounced stabilizing effects of arginine observed in the long-term storage stability study. Furthermore, the aggregation and solubility propensity predicted by commonly used <i>in silico</i> tools do not align with the preferential excipient-interaction sites identified by the MD simulations, suggesting that different physicochemical mechanisms are at play.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2427771"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623327","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}

{"title":"Seq2scFv: a toolkit for the comprehensive analysis of display libraries from long-read sequencing platforms.","authors":"Marianne Bachmann Salvy, Luca Santuari, Emanuel Schmid-Siegert, Nikolaos Lykoskoufis, Ioannis Xenarios, Bulak Arpat","doi":"10.1080/19420862.2024.2408344","DOIUrl":"10.1080/19420862.2024.2408344","url":null,"abstract":"<p><p>Antibodies have emerged as the leading class of biotherapeutics, yet traditional screening methods face significant time and resource challenges in identifying lead candidates. Integrating high-throughput sequencing with computational approaches marks a pivotal advancement in antibody discovery, expanding the antibody space to explore. In this context, a major breakthrough has been the full-length sequencing of single-chain variable fragments (scFvs) used in <i>in vitro</i> display libraries. However, few tools address the task of annotating the paired heavy and light chain variable domains (VH and VL), which is the primary advantage of full-scFv sequencing. To address this methodological gap, we introduce Seq2scFv, a novel open-source toolkit designed for analyzing <i>in vitro</i> display libraries from long-read sequencing platforms. Seq2scFv facilitates the identification and thorough characterization of V(D)J recombination in both VH and VL regions. In addition to providing annotated scFvs, translated sequences and numbered chains, Seq2scFv enables linker inference and characterization, sequence encoding with unique identifiers and quantification of identical sequences across selection rounds, thereby simplifying enrichment identification. With its versatile and standalone functionality, we anticipate that the implementation of Seq2scFv tools in antibody discovery pipelines will efficiently expedite the full characterization of display libraries and potentially facilitate the identification of high-affinity antibody candidates.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2408344"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391662","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}

{"title":"Correction.","authors":"","doi":"10.1080/19420862.2024.2416272","DOIUrl":"10.1080/19420862.2024.2416272","url":null,"abstract":"","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2416272"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469142","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}

{"title":"Targeted protein degradation through site-specific antibody conjugation with mannose 6-phosphate glycan.","authors":"Kaori Mukai, Robert Cost, Xin Sheen Zhang, Emily Condiff, Joanne Cotton, Xiaohua Liu, Ekaterina Boudanova, Björn Niebel, Peter Piepenhagen, Xinming Cai, Anna Park, Qun Zhou","doi":"10.1080/19420862.2024.2415333","DOIUrl":"10.1080/19420862.2024.2415333","url":null,"abstract":"<p><p>Recent developments in targeted protein degradation have provided great opportunities to eliminating extracellular protein targets using potential therapies with unique mechanisms of action and pharmacology. Among them, Lysosome-Targeting Chimeras (LYTACs) acting through mannose 6-phosphate receptor (M6PR) have been shown to facilitate degradation of several soluble and membrane-associated proteins in lysosomes with high efficiency. Herein we have developed a novel site-specific antibody conjugation approach to generate antibody mannose 6-phosphate (M6P) conjugates. The method uses a high affinity synthetic M6P glycan, bisM6P, that is coupled to an Fc-engineered antibody NNAS. This mutant without any effector function was generated by switching the native glycosylation site from position 297 to 298 converting non-sialylated structures to highly sialylated N-glycans. The sialic acid of the glycans attached to Asn298 in the engineered antibody was selectively conjugated to bisM6P without chemoenzymatic modification, which is often used for site-specific antibody conjugation through glycans. The conjugate is mainly homogeneous by analysis using mass spectrometry, typically with one or two glycans coupled. The M6P-conjugated antibody against a protein of interest (POI) efficiently internalized targeted soluble proteins, such as human tumor necrosis factor (TNF), in both cancer cell lines and human immune cells, through the endo-lysosomal pathway as demonstrated by confocal microscopy and flow cytometry. TNF in cell culture media was significantly depleted after the cells were incubated with the M6P-conjugated antibody. TNF internalization is mediated through M6PR, and it is correlated well with cell surface expression of cation-independent M6PR (CI-MPR) in immune cells. A significant amount of CI-MPR remains on the cell surface, while internalized TNF is degraded in lysosomes. Thus, the antibody-M6P conjugate is highly efficient in inducing internalization and subsequent lysosome-mediated protein degradation. Our platform provides a unique method for producing biologics-based degraders that may be used to treat diseases through event-driven pharmacology, thereby addressing unmet medical needs.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2415333"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469144","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}

{"title":"Insights into the mechanisms of serplulimab: a distinctive anti-PD-1 monoclonal antibody, in combination with a TIGIT or LAG3 inhibitor in preclinical tumor immunotherapy studies.","authors":"Yizhou Zhang, Ruicheng Wei, Ge Song, Xinyi Yang, Mengli Zhang, Wei Liu, Aiying Xiong, Xuehan Zhang, Qianhao Li, Wan-Jen Yang, Chencheng Han, Rui Liu, Chen Hu, Qingyu Wang, Jun Zhu, Yongqiang Shan","doi":"10.1080/19420862.2024.2419838","DOIUrl":"10.1080/19420862.2024.2419838","url":null,"abstract":"<p><p>With more than 20 anti-PD-1/PD-L1 antibodies currently marketed, anti-PD-1 therapy has become a cornerstone of tumor immunotherapy. These agents, however, exhibit notable disparities in their characteristics and clinical performance. For instance, in the field of small cell lung cancer (SCLC) where the majority of anti-PD-1 antibodies have yielded limited success, serplulimab produced impressive survival improvements and was approved for this indication by China's National Medical Products Administration. Serplulimab's marketing authorization application also received a positive opinion from the European Medicines Agency. Nevertheless, the molecular mechanism underpinning serplulimab's superiority over its competitors remains elusive. We characterized the differences between serplulimab with approved PD-1/PD-L1 inhibitors (pembrolizumab and nivolumab) in terms of their binding features and functions <i>in vitro</i> and anti-tumor activity <i>in vivo</i>. Cellular pathways underlying the efficacy of serplulimab were also investigated. In comparison to competitors, serplulimab robustly induces PD-1 receptor endocytosis while fostering weaker PD-1-CD28 cis interactions. This phenomenon could mitigate the dephosphorylation of CD28 by SHP2, thereby facilitating sustained and robust T cell activation. While serplulimab and pembrolizumab exhibited similar performance <i>in vitro</i> and <i>in vivo</i> studies, serplulimab consistently demonstrated superior tumor killing efficacy compared to pembrolizumab upon co-administration with anti-TIGIT or anti-LAG3 inhibitors. Mechanistically, the serplulimab combination effectively reduces tumor microenvironment Treg cell populations, augments effector and memory T cell populations, and more potently modulates genes associated with diverse facets of the immune system, surpassing the effects of the pembrolizumab combination. In summary, our data underscore serplulimab as a differentiated PD-1 monoclonal antibody with best-in-class therapeutic potential.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2419838"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576374","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}

{"title":"Toward enhancement of antibody thermostability and affinity by computational design in the absence of antigen.","authors":"Mark Hutchinson, Jeffrey A Ruffolo, Nantaporn Haskins, Michael Iannotti, Giuliana Vozza, Tony Pham, Nurjahan Mehzabeen, Harini Shandilya, Keith Rickert, Rebecca Croasdale-Wood, Melissa Damschroder, Ying Fu, Andrew Dippel, Jeffrey J Gray, Gilad Kaplan","doi":"10.1080/19420862.2024.2362775","DOIUrl":"10.1080/19420862.2024.2362775","url":null,"abstract":"<p><p>Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within the field of biologics. <i>In silico</i> tools that can streamline the process of antibody discovery and optimization are critical to support a pipeline that is growing more numerous and complex every year. High-quality structural information remains critical for the antibody optimization process, but antibody-antigen complex structures are often unavailable and <i>in silico</i> antibody docking methods are still unreliable. In this study, DeepAb, a deep learning model for predicting antibody Fv structure directly from sequence, was used in conjunction with single-point experimental deep mutational scanning (DMS) enrichment data to design 200 potentially optimized variants of an anti-hen egg lysozyme (HEL) antibody. We sought to determine whether DeepAb-designed variants containing combinations of beneficial mutations from the DMS exhibit enhanced thermostability and whether this optimization affected their developability profile. The 200 variants were produced through a robust high-throughput method and tested for thermal and colloidal stability (T_onset, T_m, T_agg), affinity (K_D) relative to the parental antibody, and for developability parameters (nonspecific binding, aggregation propensity, self-association). Of the designed clones, 91% and 94% exhibited increased thermal and colloidal stability and affinity, respectively. Of these, 10% showed a significantly increased affinity for HEL (5- to 21-fold increase) and thermostability (>2.5C increase in T_m1), with most clones retaining the favorable developability profile of the parental antibody. Additional <i>in silico</i> tests suggest that these methods would enrich for binding affinity even without first collecting experimental DMS measurements. These data open the possibility of <i>in silico</i> antibody optimization without the need to predict the antibody-antigen interface, which is notoriously difficult in the absence of crystal structures.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"16 1","pages":"2362775"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427121","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}