Antibody Therapeutics最新文献

{"title":"AI-based antibody discovery platform identifies novel, diverse, and pharmacologically active therapeutic antibodies against multiple SARS-CoV-2 strains.","authors":"Cristina Moldovan Loomis, Thomas Lahlali, Danielle Van Citters, Megan Sprague, Gregory Neveu, Laurence Somody, Christine C Siska, Derrick Deming, Andrew J Asakawa, Tileli Amimeur, Jeremy M Shaver, Caroline Carbonelle, Randal R Ketchem, Antoine Alam, Rutilio H Clark","doi":"10.1093/abt/tbae025","DOIUrl":"https://doi.org/10.1093/abt/tbae025","url":null,"abstract":"<p><strong>Background: </strong>We are entering a new era of antibody discovery and optimization where machine learning (ML) processes will become indispensable for the design and development of therapeutics.</p><p><strong>Methods: </strong>We have constructed a Humanoid Antibody Library for the discovery of therapeutics that is an initial step towards leveraging the utility of artificial intelligence and ML. We describe how we began our validation of the library for antibody discovery by isolating antibodies against a target of pandemic concern, SARS-CoV-2. The two main antibody quality aspects that we focused on were functional and biophysical characterization.</p><p><strong>Results: </strong>The applicability of our platform for effective therapeutic antibody discovery is demonstrated here with the identification of a panel of human monoclonal antibodies that are novel, diverse, and pharmacologically active.</p><p><strong>Conclusions: </strong>These first-generation antibodies, without the need for affinity maturation, exhibited neutralization of SARS-CoV-2 viral infectivity across multiple strains and indicated high developability potential.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FcRider: a recombinant Fc nanoparticle with endogenous adjuvant activities for hybrid immunization.","authors":"Changchuin Mao, Karen Eberle, Xiaojie Chen, Yiming Zhou, Jun Li, Hong Xin, Wenda Gao","doi":"10.1093/abt/tbae023","DOIUrl":"https://doi.org/10.1093/abt/tbae023","url":null,"abstract":"<p><p>Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8-/- CHO cells, naming it \"FcRider.\" FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those of therapeutic antibodies, and is amenable to conventional antibody purification schemes. Most importantly, FcRider possesses endogenous adjuvant activities. Using SW_HEL B cell receptor (BCR) transgenic mice, we found that HEL-FcRider induced GL7⁺ germinal center B cells and HEL-specific IgG. Similarly, immunizing mice with UFO-BG-FcRider, a fusion containing the stabilized human immunodeficiency virus-1 (HIV-1) Env protein as immunogen, promoted somatic hypermutation and generation of long CDR3 of the IgG heavy chains. Intramuscular injection of (Fba + Met6)₃-FcRider, a fusion with two peptide epitopes from <i>Candida albicans</i> cell surface, stimulated strong antigen-specific IgG titers. In three different models, we showed that afucosylated FcRider functions as a multivalent immunogen displayer and stimulates antigen-specific B cells without any exogenous adjuvant. As an antibody derivative, afucosylated FcRider could be a novel platform combining vaccines and therapeutic antibodies, integrating active and passive immunizations into single-modality \"hybrid immunization\" to provide complete and long-lasting protection against infections, and may open new avenues in cancer immunotherapy as well.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response.","authors":"Xiaofeng Niu, Chunnian Wang, Haixia Jiang, Rui Gao, Yefeng Lu, Xiaoli Guo, Hongping Zhou, Xue Cui, Jun Sun, Quan Qiu, Dawei Sun, Hongtao Lu","doi":"10.1093/abt/tbae022","DOIUrl":"https://doi.org/10.1093/abt/tbae022","url":null,"abstract":"<p><p>As a major immune cell type in the tumor microenvironment, tumor-associated macrophages secrete suppressive factors that can inhibit antitumor immunity and promote tumor progression. One approach trying to utilize macrophages for immunotherapy has been to block the CD47-SIRPα axis, which mediates inhibitory signaling, to promote phagocytosis of tumor cells. Many CD47-targeted agents, namely, anti-CD47 antibodies and SIRPα fusion proteins, were associated with a diverse spectrum of toxicities that limit their use in clinical settings. Universal expression of CD47 also leads to a severe \"antigen sink\" effect of CD47-targeted agents. Given that the CD47 receptor, SIRPα, has a more restricted expression profile and may have CD47-independent functions, targeting SIRPα is considered to have distinct advantages in improving clinical efficacy with a better safety profile. We have developed ES004-B5, a potentially best-in-class pan-allelic human SIRPα-blocking antibody using hybridoma technology. ES004-B5 binds to major human SIRPα variants through a unique epitope with high affinity. By blocking CD47-induced inhibitory \"don't-eat-me\" signaling, ES004-B5 exerts superior antitumor activity in combination with anti-tumor-associated antigen antibodies <i>in vitro</i> and <i>in vivo</i>. Unlike CD47-targeted agents, ES004-B5 exhibits an excellent safety profile in nonhuman primates. ES004-B5 has potential to be an important backbone for SIRPα-based combination therapy and/or bispecific antibodies, which will likely overcome the limitations of CD47-targeted agents encountered in clinical settings.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications.","authors":"","doi":"10.1093/abt/tbae021","DOIUrl":"https://doi.org/10.1093/abt/tbae021","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/abt/tbae013.].</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The process using a synthetic library that generates multiple diverse human single domain antibodies.","authors":"Mark A Tornetta, Brian P Whitaker, Olivia M Cantwell, Eileen D Pisors, Lu Han, Maria P MacWilliams, Hao Jiang, Fulai Zhou, Mark L Chiu","doi":"10.1093/abt/tbae020","DOIUrl":"10.1093/abt/tbae020","url":null,"abstract":"<p><strong>Background: </strong>Single domain antibodies (sdAbs) possess unique characteristics that make them highly effective for developing complex therapeutics.</p><p><strong>Methods: </strong>Our process uses a fully synthetic phage display library to generate single domain antibodies that can bind to disease relevant antigen conformations. A human IGHV3 family scaffold makes up the phage display libraries, and these VHO libraries are applied to diverse phage biopannings against target antigens. After NGS processing, unique VHOs undergo automated cloning into expression constructs followed by transfections and purifications. Binding assays were used to determine VHO binding behaviors to the target proteins. Additional VHO interactions are measured against endogenous targets on cells by way of flow cytometry, cell internalization, and activation assays.</p><p><strong>Results: </strong>We show that a fully synthetic phage display library can generate VHOs that bind to disease relevant antigen conformations. The diverse biopanning methods and processing of next-generation sequencing generated many VHO paratopes. These different VHO sequences can be expressed as Fc fusion proteins. Various screening assays resulted in VHOs representing different epitopes or activities. During the hit evaluation, we demonstrate how screening can identify distinct VHO activities that have been used to generate differentiated drug molecules in various bispecific and multispecific antibody formats.</p><p><strong>Conclusion: </strong>We demonstrate how screening can identify distinct VHO activities that have been used to generate differentiated drug molecules in various bispecific and multispecific antibody formats.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.","authors":"Michael E Dolan, Amissi Sadiki, Leo Lei Wang, Yan Wang, Christopher Barton, Sheldon F Oppenheim, Zhaohui Sunny Zhou","doi":"10.1093/abt/tbae014","DOIUrl":"https://doi.org/10.1093/abt/tbae014","url":null,"abstract":"<p><p>Despite their triumph in treating human diseases, antibody therapies for animals have gained momentum more slowly. However, the first approvals of animal antibodies for osteoarthritic pain in cats and dogs may herald the dawn of a new era. For example, goats are vital to economies around the world for their milk, meat, and hide products. It is therefore imperative to develop therapies to safeguard goats-with antibodies at the forefront. Goat antibodies will be crucial in the development of therapeutic antibodies, for example, as tracers to study antibody distribution <i>in vivo</i>, reagents to develop other therapeutic antibodies, and therapeutic agents themselves (e.g., antibody-drug conjugates). Hamstringing this effort is a still-burgeoning understanding of goat antibodies and their derivatization. Historically, goat antibody conjugates were generated through stochastic chemical modifications, producing numerous attachment sites and modification ratios, thereby deleteriously impacting antigen binding. Site-specific methods exist but often require substantial engineering and have not been demonstrated with goat antibodies. Nevertheless, we present herein a novel method to site-specifically conjugate native goat antibodies: chemo-enzymatic remodeling of the native Fc N-glycan introduces a reactive azide handle, after which click chemistry with strained alkyne partners affords homogeneous conjugates labeled only on the Fc domain. This process is robust, and resulting conjugates retain their antigen binding and specificity. To our knowledge, our report is the first for site-specific conjugation of native goat antibodies. Furthermore, our approach should be applicable to other animal antibodies-even with limited structural information-with similar success.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rAbDesFlow: A novel workflow for computational recombinant antibody design for healthcare engineering","authors":"Sowmya Ramaswamy Krishnan, Divya Sharma, Yasin Nazeer, Mayilvahanan Bose, Thangarajan Rajkumar, Guhan Jayaraman, Narayanan Madaboosi, M. M. Gromiha","doi":"10.1093/abt/tbae018","DOIUrl":"https://doi.org/10.1093/abt/tbae018","url":null,"abstract":"\u0000 \u0000 \u0000 Recombinant antibodies have emerged as a promising solution to tackle antigen specificity, enhancement of immunogenic potential and versatile functionalization to treat human diseases. The development of single chain variable fragments (scFv) has helped accelerate treatment in cancers and viral infections, due to their favorable pharmacokinetics and human compatibility. However, designing recombinant antibodies is traditionally viewed as a genetic engineering problem, with phage display and cell free systems playing a major role in sequence selection for gene synthesis. The process of antibody engineering involves complex and time-consuming laboratory techniques, which demand substantial resources and expertise. The success rate of obtaining desired antibody candidates through experimental approaches can be modest, necessitating iterative cycles of selection and optimization. With ongoing advancements in technology, in silico design of diverse antibody libraries, screening and identification of potential candidates for in vitro validation can be accelerated.\u0000 \u0000 \u0000 \u0000 To meet this need, we have developed rAbDesFlow, a unified computational workflow for recombinant antibody engineering with open-source programs and tools for ease of implementation.\u0000 \u0000 \u0000 \u0000 The workflow encompasses five computational modules to perform antigen selection, antibody library generation, antigen and antibody structure modeling, antigen-antibody interaction modeling, structure analysis, and consensus ranking of potential antibody sequences for synthesis and experimental validation. The proposed workflow has been demonstrated through design of recombinant antibodies for the ovarian cancer antigen Mucin-16 (CA-125).\u0000 \u0000 \u0000 \u0000 This approach can serve as a blueprint for designing similar engineered molecules targeting other biomarkers, allowing for a simplified adaptation to different cancer types or disease-specific antigens.\u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141668754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBsAg and TLR7/8 dual-targeting antibody-drug conjugates induce sustained anti-HBV activity in AAV/HBV mice: a preliminary study","authors":"Xinya Ye, Xiaoqing Chen, Han Liu, Yichao Jiang, Chengyu Yang, Tao Xu, Ziyou Chen, Yalin Wang, Fentian Chen, Xue Liu, Hai Yu, Quan Yuan, Ningshao Xia, Yuanzhi Chen, Wenxin Luo","doi":"10.1093/abt/tbae016","DOIUrl":"https://doi.org/10.1093/abt/tbae016","url":null,"abstract":"\u0000 \u0000 \u0000 Hepatitis B virus (HBV) infection is a significant global health concern due to elevated immunosuppressive viral antigen levels, the host immune system’s inability to manage HBV, and the liver’s immunosuppressive conditions. While immunotherapies utilizing broadly reactive HBV neutralizing antibodies (nAbs) present potential due to their antiviral capabilities and Fc-dependent vaccinal effects, they necessitate prolonged and frequent dosing to achieve optimal therapeutic outcomes. Toll-like receptor 7/8 (TLR7/8) agonists have been demonstrated promise for the cure of chronic hepatitis B (CHB), but their systemic use often leads to intense side effects. In this study, we introduced immune-stimulating antibody conjugates (ISACs) which consist of TLR7/8 agonists 1-[[4-(aminomethyl)phenyl]methyl]-2-butyl-imidazo[4,5-c]quinolin-4-amine (IMDQ) linked to an anti-HBsAg antibody 129G1, and designated as 129G1-IMDQ. Our preliminary study highlights that 129G1-IMDQ can prompt robust and sustained anti-HBsAg specific reactions with short-term administration. This underscores the conjugate’s potential as an effective strategy for HBsAg clearance and seroconversion, offering a fresh perspective for a practical therapeutic approach in the functional cure of CHB.\u0000 \u0000 \u0000 \u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141680503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity.","authors":"Yang Wang, Bing Xia, Lixia Cao, Jianfeng Yang, Cui Feng, Fangdun Jiang, Chen Li, Lixia Gu, Yifan Yang, Jing Tian, Xin Cheng, Keiji Furuuchi, James Fulmer, Arielle Verdi, Katherine Rybinski, Allis Soto, Earl Albone, Toshimitsu Uenaka, Likun Gong, Tingting Liu, Qiuping Qin, Ziping Wei, Yuhong Zhou","doi":"10.1093/abt/tbae019","DOIUrl":"10.1093/abt/tbae019","url":null,"abstract":"<p><strong>Background: </strong>Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins. Eribulin, a therapeutic agent for the treatment of metastatic breast cancer and liposarcoma, is a new choice of ADC payload with a distinct mechanism of action and safety profile.</p><p><strong>Methods: </strong>We've generated a novel HER2-tageting eribulin-containing ADC, BB-1701. The potency of BB-1701 was tested <i>in vitro</i> and <i>in vivo</i> against cancer cells where HER2-expressing levels vary in a large range. Bystander killing effect and toxin-induced immunogenic cell death (ICD) of BB-1701 were also tested.</p><p><strong>Results: </strong>In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher <i>in vitro</i> cytotoxicity in HER2-low cancer cell lines. BB-1701 also effectively suppressed tumors in models resistant to DM1 or Dxd containing ADCs. Mode of action studies showed that BB-1701 had a significant bystander effect on HER2-null cells adjacent to HER2-high cells. In addition, BB-1701 treatment induced ICD. Repeated doses of BB-1701 in nonhuman primates showed favorable pharmacokinetics and safety profiles at the intended clinical dosage, route of administration, and schedule.</p><p><strong>Conclusions: </strong>The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fc engineering by monoclonal mammalian cell display for improved affinity and selectivity towards FcγRs.","authors":"Zening Wang, Minhyo Kang, Afshin Ebrahimpour, Chuan Chen, Xin Ge","doi":"10.1093/abt/tbae017","DOIUrl":"10.1093/abt/tbae017","url":null,"abstract":"<p><p>Fc optimization can significantly enhance therapeutic efficacy of monoclonal antibodies. However, existing Fc engineering approaches are sub-optimal with noted limitations, such as inappropriate glycosylation, polyclonal libraries, and utilizing fragment but not full-length IgG display. Applying cell cycle arrested recombinase-mediated cassette exchange, this study constructed high-quality monoclonal Fc libraries in CHO cells, displayed full-length IgG on cell surface, and preformed ratiometric fluorescence activated cell sorting (FACS) with the antigen and individual FcγRs. Identified Fc variants were quantitatively evaluated by flow cytometry, ELISA, kinetic and steady-state binding affinity measurements, and cytotoxicity assays. An error-prone Fc library focusing on the hinge-C_H2 region was constructed in CHO cells with a functional diversity of 7.5 × 10⁶. Panels of novel Fc variants with enhanced affinity and selectivity for FcγRs were isolated. Particularly, clone 2a-10 (G236E/K288R/K290W/K320M) showed increased binding strength towards FcγRIIa-131R and 131H allotypes with kinetic dissociation constants (K_D-K) of 140 nM and 220 nM, respectively, while reduced binding strength towards FcγRIIb compared to WT Fc; clone 2b-1 (K222I/V302E/L328F/K334E) had K_D-K of 180 nM towards FcγRIIb; clone 3a-2 (P247L/K248E/K334I) exhibited K_D-K of 190 nM and 100 nM towards FcγRIIIa-176F and 176 V allotypes, respectively, and improved potency of 2.0 ng/ml in ADCC assays. Key mutation hotspots were identified, including P247 for FcγRIIIa, K290 for FcγRIIa, and K334 for FcγRIIb bindings. Discovery of Fc variants with enhanced affinity and selectivity towards individual FcγR and the identification of novel mutation hotspots provide valuable insights for further Fc optimization and serve as a foundation for advancing antibody therapeutics development.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}