Antibody Therapeutics最新文献_第3页

Correction to: Bringing cell therapy to tumors: considerations for optimal CAR binder design 更正：为肿瘤带来细胞疗法：最佳 CAR 粘合剂设计的考虑因素

Antibody Therapeutics Pub Date : 2024-02-14 DOI: 10.1093/abt/tbae003

引用次数: 0

Understanding the pharmacokinetic journey of fc-fusion protein, rhIL-7-hyFc, using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA 利用加速器质谱法和酶联免疫吸附法这两种分析方法的互补方法了解 fc 融合蛋白 rhIL-7-hyFc 的药代动力学历程

Antibody Therapeutics Pub Date : 2024-02-06 DOI: 10.1093/abt/tbae004

Anhye Kim, Min-Seok Oh, Gwan-Ho Lee, Seongeun Song, Mi-sun Byun, Donghoon Choi, Byung-Yong Yu, Howard Lee

{"title":"Understanding the pharmacokinetic journey of fc-fusion protein, rhIL-7-hyFc, using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA","authors":"Anhye Kim, Min-Seok Oh, Gwan-Ho Lee, Seongeun Song, Mi-sun Byun, Donghoon Choi, Byung-Yong Yu, Howard Lee","doi":"10.1093/abt/tbae004","DOIUrl":"https://doi.org/10.1093/abt/tbae004","url":null,"abstract":"\u0000 \u0000 \u0000 Antibody-based therapeutics (ABTs) including monoclonal/polyclonal antibodies and Fc-fusion proteins are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS).\u0000 \u0000 \u0000 \u0000 Total 4 rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. TRA concentrations in organs were determined by AMS.\u0000 \u0000 \u0000 \u0000 Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc’s affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method.\u0000 \u0000 \u0000 \u0000 Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification, as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offer valuable insights for the development and optimization of ABT.\u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139800525","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}

引用次数: 0

Understanding the pharmacokinetic journey of fc-fusion protein, rhIL-7-hyFc, using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA 利用加速器质谱法和酶联免疫吸附法这两种分析方法的互补方法了解 fc 融合蛋白 rhIL-7-hyFc 的药代动力学历程

Antibody Therapeutics Pub Date : 2024-02-06 DOI: 10.1093/abt/tbae004

Anhye Kim, Min-Seok Oh, Gwan-Ho Lee, Seongeun Song, Mi-sun Byun, Donghoon Choi, Byung-Yong Yu, Howard Lee

{"title":"Understanding the pharmacokinetic journey of fc-fusion protein, rhIL-7-hyFc, using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA","authors":"Anhye Kim, Min-Seok Oh, Gwan-Ho Lee, Seongeun Song, Mi-sun Byun, Donghoon Choi, Byung-Yong Yu, Howard Lee","doi":"10.1093/abt/tbae004","DOIUrl":"https://doi.org/10.1093/abt/tbae004","url":null,"abstract":"\u0000 \u0000 \u0000 Antibody-based therapeutics (ABTs) including monoclonal/polyclonal antibodies and Fc-fusion proteins are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS).\u0000 \u0000 \u0000 \u0000 Total 4 rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. TRA concentrations in organs were determined by AMS.\u0000 \u0000 \u0000 \u0000 Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc’s affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method.\u0000 \u0000 \u0000 \u0000 Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification, as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offer valuable insights for the development and optimization of ABT.\u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139860662","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}

引用次数: 0

Further Accelerating Biologics Development from DNA to IND: The Journey from COVID-19 to Non-COVID-19 Programs 进一步加快从 DNA 到 IND 的生物制剂开发：从 COVID-19 到非 COVID-19 计划的历程

Antibody Therapeutics Pub Date : 2024-01-24 DOI: 10.1093/abt/tbae001

Kee Wee Tan, Pengfei Ji, Hang Zhou, Sam Zhang, Weichang Zhou

引用次数: 0

Effects of fc glycosylation on the activity of WNT mimetic agonistic antibodies fc 糖基化对 WNT 拟态激动抗体活性的影响

Antibody Therapeutics Pub Date : 2024-01-18 DOI: 10.1093/abt/tbae002

Hui Chen, Sung-Jin Lee, Brian Ouyang, Nicholas Suen, Jay Ye, Cheng-yu Lu, Yang Li

引用次数: 0

GB12–09, a bispecific antibody targeting IL4Rα and IL31Rα for atopic dermatitis therapy 用于特应性皮炎治疗的靶向 IL4Rα 和 IL31Rα 的双特异性抗体 GB12-09

Antibody Therapeutics Pub Date : 2024-01-05 DOI: 10.1093/abt/tbad032

Feiyan Deng, Yuxin Qiu, Xiangling Zhang, Nining Guo, Junhong Hu, Wenjie Yang, Wei Shang, Bicheng Liu, Suofu Qin

{"title":"GB12–09, a bispecific antibody targeting IL4Rα and IL31Rα for atopic dermatitis therapy","authors":"Feiyan Deng, Yuxin Qiu, Xiangling Zhang, Nining Guo, Junhong Hu, Wenjie Yang, Wei Shang, Bicheng Liu, Suofu Qin","doi":"10.1093/abt/tbad032","DOIUrl":"https://doi.org/10.1093/abt/tbad032","url":null,"abstract":"\u0000 \u0000 \u0000 Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by dysregulated immune responses. The key mediators of AD pathogenesis are T helper 2 (TH2) cells and TH2 cytokines. Targeting interleukin 4 (IL4), IL13, or IL31 has become a pivotal focus in both research and clinical treatments for AD. However, the need remains pressing for the development of a more effective and safer therapy, as the current approaches often yield low response rates and adverse effects.\u0000 \u0000 \u0000 \u0000 In response to this challenge, we have engineered an IgG-scFv (Immunoglobulin G—single-chain Fragment variable) format bispecific antibody designed to concurrently target IL4R and IL31R. Our innovative design involved sequence optimization of VL-VH and the introduction of disulfide bond (VH44-VL100) within the IL31Rα antibody scFv region to stabilize the scFv structure.\u0000 \u0000 \u0000 \u0000 Our bispecific antibody efficiently inhibited the IL4/IL13/IL31 signaling pathways in vitro and reduced serum Immunoglobulin E (IgE) and IL31 levels in vivo. Consequently, this intervention led to improved inflammation profiles and notable amelioration of AD symptoms.\u0000 \u0000 \u0000 \u0000 This research highlighted a novel approach to AD therapy by employing bispecific antibody targeting IL4Rα and IL31Rα with potent efficacy.\u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139382968","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}

引用次数: 0

Multiple approaches to reduce reconstitution time of lyophilized drug products with high protein concentration 减少高蛋白冻干药品复溶时间的多种方法

Antibody Therapeutics Pub Date : 2023-12-29 DOI: 10.1093/abt/tbad031

Xiaozhang Zhang, Ningning Zhou, Chunsheng Yang, Zhaowei Jin, Jeremy Guo

{"title":"Multiple approaches to reduce reconstitution time of lyophilized drug products with high protein concentration","authors":"Xiaozhang Zhang, Ningning Zhou, Chunsheng Yang, Zhaowei Jin, Jeremy Guo","doi":"10.1093/abt/tbad031","DOIUrl":"https://doi.org/10.1093/abt/tbad031","url":null,"abstract":"Lyophilized drug products with high protein concentration often perform long reconstitution time, which is inconvenient for clinical use. The objective of this work is to achieve short reconstitution time with multiple and combined strategies. In this paper, we describe the following approaches that lead to reduction of reconstitution time. In terms of lyophilization process, using annealing step during freezing can increase the pore size of lyophilized cake, and decreasing headspace pressure in vial before stoppering can also help solvent penetrate through lyophilized cake. Regarding to formulations, it is an effective strategy of decreasing protein concentration or reducing diluent volume to achieve high protein concentration after reconstitution. Considering container size, high surface-area-to-height ratio of the cakes is also beneficial for reduction of reconstitution time. In addition, reconstitution methods, for example, increasing frequency of swirling and diluent temperature are also helpful to reduce reconstitution time. Among these strategies, reducing diluent volume to achieve high protein concentration and reducing headspace pressure show markedly reduction of reconstitution time. Moreover, we propose combined strategies to mitigate the reconstitution time, at the same time, to achieve same target dose in clinics. The combination of all factors can achieve the overall reduction ratio of 98%, and will not influence the product quality. Therefore, this paper provides insights on the application of multiple strategies to accelerate the reconstitution of lyophilized drug products with high concentration, and facilitates their widespread clinical application.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139146021","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}

引用次数: 0

ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: A quick therapeutic option for current and future coronaviruses outbreaks 针对 SARS-CoV-2 和 MERS-CoV 变种的 ACE2-Fc 和 DPP4-Fc 诱饵受体：应对当前和未来冠状病毒爆发的快速治疗方案

Antibody Therapeutics Pub Date : 2023-12-12 DOI: 10.1093/abt/tbad030

M. Alfaleh, R. Alsulaiman, S. Almahboub, Leena Nezamuldeen, A. Zawawi, Najwa D. Aljehani, Muhammad Yasir, Rwaa H Abdulaal, Rami Alkhaldi, Assala Helal, S. S. Alamri, Jana S. Malki, R. Alhabbab, T. Abujamel, Nabil A Alhakamy, Aisha Alnami, A. Algaissi, Mazen Hassanain, A. Hashem

{"title":"ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: A quick therapeutic option for current and future coronaviruses outbreaks","authors":"M. Alfaleh, R. Alsulaiman, S. Almahboub, Leena Nezamuldeen, A. Zawawi, Najwa D. Aljehani, Muhammad Yasir, Rwaa H Abdulaal, Rami Alkhaldi, Assala Helal, S. S. Alamri, Jana S. Malki, R. Alhabbab, T. Abujamel, Nabil A Alhakamy, Aisha Alnami, A. Algaissi, Mazen Hassanain, A. Hashem","doi":"10.1093/abt/tbad030","DOIUrl":"https://doi.org/10.1093/abt/tbad030","url":null,"abstract":"\u0000 \u0000 \u0000 The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic human coronaviruses (CoVs). Anti-CoVs mAbs and vaccines may be effective, but the emergence of neutralization escape variants is inevitable.\u0000 \u0000 \u0000 \u0000 Angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 enzyme (DPP4) are the getaway receptors for SARS-CoV-2 and MERS-CoV, respectively. Thus, we reformatted these receptors and expressed them as recombinant Fc-fusion decoy receptors. Then we tested them in parallel with anti-SARS-CoV (ab1-IgG) and anti-MERS-CoV (M336-IgG) mAbs in ELISA and against several pseudotyped SARS-CoV-2 and MERS-CoV variants using pseudovirus neutralization assay.\u0000 \u0000 \u0000 \u0000 The generated Fc-based decoy receptors exhibited a strong inhibitory effect against all pseudotyped CoVs. Results showed that although mAbs can be effective antiviral drugs, they might rapidly lose their efficacy against highly mutated viruses, as shown with ab1-IgG against some of the SARS-CoV-2 variants.\u0000 \u0000 \u0000 \u0000 We suggest that receptor traps can be engineered as Fc-fusion proteins for highly mutating viruses with known entry receptors, for a faster and effective therapeutic response even against virus harboring antibodies escape mutations.\u0000","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138977196","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}

引用次数: 0

Next generation of multispecific antibody engineering 新一代多特异性抗体工程

Antibody Therapeutics Pub Date : 2023-12-08 DOI: 10.1093/abt/tbad027

Daniel Keri, Matt Walker, Isha Singh, Kyle Nishikawa, Fernando Garces

引用次数: 0

CD80-fc fusion protein as a potential cancer immunotherapy strategy 将 CD80-fc 融合蛋白作为一种潜在的癌症免疫疗法策略

Antibody Therapeutics Pub Date : 2023-11-30 DOI: 10.1093/abt/tbad029

Songna Wang, Pinliang Hu, Jiajun Fan, Jing Zou, Weidong Hong, Xuan Huang, Dan-Ling Pan, Huaning Chen, Yi Zhun Zhu, Liping Ye

{"title":"CD80-fc fusion protein as a potential cancer immunotherapy strategy","authors":"Songna Wang, Pinliang Hu, Jiajun Fan, Jing Zou, Weidong Hong, Xuan Huang, Dan-Ling Pan, Huaning Chen, Yi Zhun Zhu, Liping Ye","doi":"10.1093/abt/tbad029","DOIUrl":"https://doi.org/10.1093/abt/tbad029","url":null,"abstract":"The activation of T lymphocytes is a crucial component of the immune response, and the presence of CD80, a membrane antigen, is necessary for T-cell activation. CD80 is usually expressed on antigen-presenting cells (APCs), which can interact with cluster of differentiation 28 (CD28) or programmed cell death ligand 1 (PD-L1) to promote T-cell proliferation, differentiation and function by activating costimulatory signal or blocking inhibitory signal. Simultaneously, CD80 on the APCs also interacts with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells to suppress the response of specific effector T cells, particularly in the context of persistent antigenic stimulation. Due to the pivotal role of CD80 in the immune response, the CD80-Fc fusion protein has emerged as a promising approach for cancer immunotherapy. This review primarily focused on the crucial role of CD80 in the cancer immunotherapy. We also reviewed the current advancements in the research of CD80-Fc fusion proteins. Finally, we deliberated on the challenges encountered by CD80-Fc fusion proteins and proposed the potential strategies that could yield the benefits for patients.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139205249","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}

引用次数: 0