Antibody Therapeutics最新文献

Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development. 抗体-药物偶联物配方开发的基本特性和主要关注领域。

Antibody Therapeutics Pub Date : 2025-03-09 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf005

Lili Wen, Yuanyuan Zhang, Chenxi Sun, Shawn Shouye Wang, Yuhui Gong, Chunyuan Jia, Jianjun Luo

{"title":"Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development.","authors":"Lili Wen, Yuanyuan Zhang, Chenxi Sun, Shawn Shouye Wang, Yuhui Gong, Chunyuan Jia, Jianjun Luo","doi":"10.1093/abt/tbaf005","DOIUrl":"10.1093/abt/tbaf005","url":null,"abstract":"Antibody-drug conjugates (ADCs) have emerged as a rapidly expanding class of therapeutics driven by their superior specificity and clinical efficacy. 14 out of 16 commercially approved ADCs are formulated as lyophilized forms because ADC is generally considered to be less stable than unmodified antibody. The formulation development for ADCs, particularly liquid formulation, presents unique challenges due to their intricate structural complexity, physicochemical properties, and degradation pathways. This review provides the first comprehensive analysis of formulation strategies employed in commercial ADCs. Furthermore, this review discusses the key areas of focus for ADCs throughout the formulation development workflow, spanning from the initial formulation development to the final stage of drug product manufacturing. In addition, we identify and analyze the distinctive technical challenges in ADC formulation development compared to unconjugated antibody, while proposing potential solutions to these challenges. Finally, we offer strategic perspectives on future directions in ADC formulation development to advance this promising therapeutic modality.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"99-110"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774573","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}

引用次数: 0

A systematic review of the avian antibody (IgY) therapeutic effects on human bacterial infections over the decade. 近十年来禽抗体（IgY）治疗人细菌感染效果的系统综述。

Antibody Therapeutics Pub Date : 2025-03-09 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf007

Zahra Esmaeili, Sara Kamal Shahsavar, Kiarash Ghazvini

{"title":"A systematic review of the avian antibody (IgY) therapeutic effects on human bacterial infections over the decade.","authors":"Zahra Esmaeili, Sara Kamal Shahsavar, Kiarash Ghazvini","doi":"10.1093/abt/tbaf007","DOIUrl":"10.1093/abt/tbaf007","url":null,"abstract":"The overuse of antibiotics worldwide, especially during the Coronavirus pandemic, has raised concerns about the rise of antibiotic resistance and its side effects. Immunoglobulin Y, a natural protein that specifically targets foreign antigens, holds promise as a potential therapeutic option, particularly for individuals with sensitive immune systems. Despite numerous studies on IgY, the optimal administration method, effective dose, target antigen, and potential side effects of this antibody remain areas of active research and challenge. This review selected and evaluated articles published in the last ten years from databases such as PubMed and Science Direct with appropriate keywords discussing the therapeutic effects of immunoglobulin Y in human infections in vivo. Out of all the reviewed articles, 35 articles met the inclusion criteria. The results showed that the specific antibody against dental, respiratory, and skin infections has an acceptable effectiveness. In contrast, some infections, such as neurological infections, including tetanus and botulism, still need further investigation due to the short survival time of mice. On the other hand, reporting side effects such as antibody-dependent enhancement in some infections limits its use.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"111-123"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774483","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}

引用次数: 0

Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality. 抗体治疗中的Fc γ受体多态性：对提高产品质量的生物测定发展的影响。

Antibody Therapeutics Pub Date : 2025-01-21 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf003

Julianne D Twomey, Sasha George, Baolin Zhang

引用次数: 0

Near-infrared photoimmunotherapy: mechanisms, applications, and future perspectives in cancer research. 近红外光免疫疗法：在癌症研究中的机制、应用和未来展望。

Antibody Therapeutics Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbaf001

Derek Allen, Madeline JoAnna Szoo, Tessa D van Bergen, Ani Seppelin, Jeonghyun Oh, Mohammad A Saad

{"title":"Near-infrared photoimmunotherapy: mechanisms, applications, and future perspectives in cancer research.","authors":"Derek Allen, Madeline JoAnna Szoo, Tessa D van Bergen, Ani Seppelin, Jeonghyun Oh, Mohammad A Saad","doi":"10.1093/abt/tbaf001","DOIUrl":"10.1093/abt/tbaf001","url":null,"abstract":"Photoimmunotherapy (PIT) involves the targeted delivery of a photosensitizer through antibody conjugation, which, upon binding to its cellular target and activation by external irradiation, induces localized toxicity. This approach addresses several limitations of conventional cancer therapies, such as chemo- and radiotherapies, which result in off-target effects that significantly reduce patient quality of life. Furthermore, PIT improves on the challenges encountered with photodynamic therapy (PDT), such as nonspecific localization of the photosensitizer, which often results in unintended toxicities. Although PIT was first proposed in the early 1980s, its clinical applications have been constrained by limitations in antibody engineering, conjugation chemistries, and optical technologies. However, recent advances in antibody-drug conjugate (ADC) research and the emergence of sophisticated laser technologies have greatly benefited the broader applicability of PIT. Notably, the first near-infrared photoimmunotherapy (NIR-PIT) treatment for head and neck cancer has been approved in Japan and is currently in phase III clinical trials in the USA. A significant advantage of PIT over traditional ADCs in cancer management is the agnostic nature of PDT, making it more adaptable to different tumor types. Specifically, PIT can act on cancer stem cells and cancer cells displaying treatment resistance and aggressive phenotypes-a capability beyond the scope of ADCs alone. This review provides an overview of the mechanism of action of NIR-PIT, highlighting its adaptability and application in cancer therapeutics, and concludes by exploring the potential of PIT in advancing cancer treatments.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"68-85"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433820","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}

引用次数: 0

Generation of antagonistic biparatopic anti-CD30 antibody from an agonistic antibody by precise epitope determination and utilization of structural characteristics of CD30 molecule. 利用CD30分子的结构特征，精确确定抗原表位，从拮抗抗体中生成拮抗双异位抗CD30抗体。

Antibody Therapeutics Pub Date : 2025-01-14 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbaf002

Hiroki Akiba, Tomoko Ise, Reiko Satoh, Yasuhiro Abe, Kouhei Tsumoto, Hiroaki Ohno, Haruhiko Kamada, Satoshi Nagata

{"title":"Generation of antagonistic biparatopic anti-CD30 antibody from an agonistic antibody by precise epitope determination and utilization of structural characteristics of CD30 molecule.","authors":"Hiroki Akiba, Tomoko Ise, Reiko Satoh, Yasuhiro Abe, Kouhei Tsumoto, Hiroaki Ohno, Haruhiko Kamada, Satoshi Nagata","doi":"10.1093/abt/tbaf002","DOIUrl":"10.1093/abt/tbaf002","url":null,"abstract":"Background: CD30 is a member of the tumor necrosis factor receptor superfamily. Recently, blocking CD30-dependent intracellular signaling has emerged as potential strategy for immunological regulation. Development of antibody-based CD30 antagonists is therefore of significant interest. However, a key challenge is that the bivalent form of natural antibody can crosslink CD30 molecules, leading to signal transduction even in the absence of specific ligand, CD153. Biparatopic antibodies (BpAbs) offer a solution, using two different variable fragments (Fvs) to bind distinct epitopes on a single antigen molecule. BpAbs format is an attractive alternative of natural antibody by potentially avoiding unwanted crosslinking and signaling induction.Methods: We systematically characterized 36 BpAbs, each designed with pairs of Fvs binding to nine distinct epitopes across the CD30 extracellular domain. We first identified the precise epitope sites of the nine antibodies by assessing the binding to multiple orthologous CD30 proteins and mutants. We then produced the 36 BpAbs and analyzed their biological activities and binding modes.Results: Among 36 BpAbs, we identified both potent ligand-independent agonists and ligand-blocking antagonists, with many displayed reduced signal activation, including 1:1-binding antagonists derived from AC10, a strong agonist developed for lymphoma therapy. Epitope dependency in reduced signaling activity was observed and associated with the flexible nature of CD30 protein.Conclusions: We successfully developed antagonistic BpAbs against CD30 by controlling the stoichiometry of antibody-antigen binding mode. This study elucidated the mechanism of signaling induction, informing the design strategies of the development of biparatopic antibodies.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"56-67"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433819","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}

引用次数: 0

Current use and development of monoclonal antibodies for the treatment of systemic lupus erythematosus: a review. 单克隆抗体治疗系统性红斑狼疮的现状及进展综述。

Antibody Therapeutics Pub Date : 2024-12-26 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbae033

Alexander Blagov, Nikolay Orekhov, Alexey Churov, Irina Starodubtseva, Dmitry Beloyartsev, Tatiana Kovyanova, Vasily Sukhorukov, Alexander Orekhov

引用次数: 0

A bioluminescent reporter bioassay for in-process assessment of chimeric antigen receptor lentiviral vector potency. 一种用于嵌合抗原受体慢病毒载体效价评估的生物发光报告生物测定法。

Antibody Therapeutics Pub Date : 2024-12-19 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbae032

Julia K Gilden, Pete Stecha, Jim Hartnett, Mei Cong

{"title":"A bioluminescent reporter bioassay for in-process assessment of chimeric antigen receptor lentiviral vector potency.","authors":"Julia K Gilden, Pete Stecha, Jim Hartnett, Mei Cong","doi":"10.1093/abt/tbae032","DOIUrl":"10.1093/abt/tbae032","url":null,"abstract":"Background: Chimeric antigen receptor (CAR)-T-cell therapy is a breakthrough in the field of cancer immunotherapy, wherein T cells are genetically modified to recognize and attack cancer cells. Delivery of the CAR gene is a critical step in this therapy and is usually achieved by transducing patient T cells with a lentiviral vector (LV). Because the LV is an essential component of CAR-T manufacturing, there is a need for simple bioassays that reflect the mechanism of action (MOA) of the LV and can measure LV potency with accuracy and specificity. Common methods for LV quantification may overestimate functional titer and lack a functional readout of LV MOA.Methods: We developed a bioluminescent reporter bioassay using Jurkat T cells stably expressing a luciferase reporter under the control of an nuclear factor of activated T cells (NFAT) response element and tested its suitability for measuring LV potency.Results: Jurkat reporter cells can be transduced with CAR LV and combined with target cells, yielding a luminescent signal that is dependent on the identity and potency of the LV used. Bioluminescence was highly correlated with CAR expression. The assay is stability indicating and suitable for use in drug development and quality control settings.Conclusions: We have developed a simple bioassay for potency testing of CAR LV. The bioassay represents a significant improvement over other approaches to LV quantification because it reflects the MOA of the LV and selectively detects fully functional viral particles, making it ideal for inclusion in a matrix of in-process quality control assays for CAR LV.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"40-46"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013439","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}

引用次数: 0

Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications. 适合基础研究和治疗应用的人源抗cd11d单克隆抗体。

Antibody Therapeutics Pub Date : 2024-12-16 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbae031

Eoin N Blythe, Christy Barreira, Corby Fink, Arthur Brown, Lynne C Weaver, Gregory A Dekaban

{"title":"Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications.","authors":"Eoin N Blythe, Christy Barreira, Corby Fink, Arthur Brown, Lynne C Weaver, Gregory A Dekaban","doi":"10.1093/abt/tbae031","DOIUrl":"10.1093/abt/tbae031","url":null,"abstract":"Background: Immunomodulatory agents targeting the CD11d/CD18 integrin are in development for the treatment of several pathophysiologies including neurotrauma, sepsis, and atherosclerosis. Murine anti-human CD11d therapeutic antibodies have successfully improved neurological and behavioral recovery in rodent neurotrauma models. Here, we present the progression of CD11d-targeted agents with the development of humanized anti-CD11d monoclonal antibodies.Methods: Primary human leukocytes and the THP-1 monocytic cell line were used to determine the binding of the CD11d antibodies, determine binding affinities, and assess outside-in signaling induced by CD11d antibody binding. In addition, a rat model of spinal cord injury was employed to demonstrate that the humanized monoclonal antibodies retained their therapeutic function in vivo. These determinations were made using a combination of flow cytometry, western blotting, immunohistochemistry, biochemical assays, and a locomotor behavioral assessment.Results: Flow cytometric analysis demonstrated that the humanized anti-CD11d clones bind both human monocytes and neutrophils. Using a THP-1 model, the humanized anti-CD11d-2 clone was then determined to bind both the active and inactive CD11d/CD18 conformations without inducing inflammatory cell signaling. Finally, an investigation using anti-CD11d-2 as a detection tool uncovered a mismatch between total and surface-level CD11d and CD18 expression that was not altered by CK2 inhibition.Conclusions: By developing humanized anti-CD11d monoclonal antibodies, new tools are now available to study CD11d biology and potentially treat inflammation arising from acute neurotrauma via CD11d targeting.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"26-39"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013374","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}

引用次数: 0

Practical advice in the development of a lyophilized protein drug product. 冻干蛋白药品开发中的实用建议。

Antibody Therapeutics Pub Date : 2024-11-21 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbae030

Yuan Cheng, Huu Thuy Trang Duong, Qingyan Hu, Mohammed Shameem, Xiaolin Charlie Tang

{"title":"Practical advice in the development of a lyophilized protein drug product.","authors":"Yuan Cheng, Huu Thuy Trang Duong, Qingyan Hu, Mohammed Shameem, Xiaolin Charlie Tang","doi":"10.1093/abt/tbae030","DOIUrl":"10.1093/abt/tbae030","url":null,"abstract":"The development of lyophilized protein drug products is a critical and complex task in the pharmaceutical industry, requiring a comprehensive understanding of the myriad of factors affecting product quality, stability, and the efficiency and robustness of the lyophilization process. This review offers practical advice on the critical aspects of lyophilized protein drug product development. Practical considerations across both the early and late stages of development are discussed, underscoring the necessity of a strategic approach from initial development through to commercialization. The review then delves into formulation optimization strategies that are essential for enhancing protein stability and the efficiency of the lyophilization process. This section outlines stable formulation design and highlights the unique considerations required for high protein concentration lyophilized drug products. It further explores the formulation strategies to enhance the lyophilization process' efficiency. Moreover, the paper examines the critical elements in selecting primary containers and closures for lyophilized drug products, focusing on vials and dual chamber systems. The analysis encompasses the effects of the container/closure's material, size, geometry, and fill volume on product quality and process efficiency. Lastly, the review provides practical considerations in lyophilization cycle development, including the design and optimization of the freezing, primary drying, and secondary drying stages to achieve a robust, scalable, and efficient lyophilization process. By offering comprehensive insights into these key areas to enhance their understanding and implementation of best practices in the field, this paper serves as a useful resource for researchers, formulators, and process engineers involved in the development of lyophilized protein drug products.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"13-25"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013379","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}

引用次数: 0

Connexin 43 hemichannels and related diseases. 连接蛋白 43 半通道和相关疾病。

Antibody Therapeutics Pub Date : 2024-11-11 eCollection Date: 2024-10-01 DOI: 10.1093/abt/tbae024

Yanfeng Zhang, Francisca M Acosta, Jean X Jiang

引用次数: 0