Antibodies最新文献

{"title":"Future Landscape of Anti-Claudin 18.2 Antibodies in Gastric Adenocarcinoma.","authors":"Wendy M Covert, Jane E Rogers","doi":"10.3390/antib14010026","DOIUrl":"10.3390/antib14010026","url":null,"abstract":"<p><p>Advanced gastric adenocarcinoma (GAC) carries a poor prognosis. Targeted therapy in GAC has traditionally been limited to anti-human epidermal growth factor receptor-2 and anti-vascular endothelial growth factor agents. Recent years have brought immune checkpoint therapy to the GAC treatment landscape. However, continued discovery of targeted therapy in GAC is needed. Claudins, transmembrane proteins located in tight junctions of epithelial and endothelial cells, help regulate cellular polarity. Claudin dysregulation has been linked to cancers and other diseases. Claudin 18.2 specifically has become a new novel and exciting biomarker for GAC. Many agents are in the investigative pipeline, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric T-cell therapy. Recently, zolbetuximab, an anti-claudin 18.2 monoclonal antibody, was the first of these agents to get FDA approval. Here, we review zolbetuximab's place in therapy along with other agents being explored.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708282","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":"Is There a Diagnostic and Prognostic Role for Anti-Nephrin Autoantibodies in Diabetic Nephropathy?","authors":"Han Sean Lee, Henry H L Wu, Arvind Ponnusamy, Helen Alderson, Rajkumar Chinnadurai","doi":"10.3390/antib14010025","DOIUrl":"10.3390/antib14010025","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is one of the key causes of end-stage kidney disease worldwide, especially in developed countries. The classic pathogenic development of DN is characterized by microalbuminuria which would progress to nephrotic-range proteinuria and loss of kidney function. The degree of albuminuria is considered an independent risk factor for all-cause mortality in patients with DN. It is now well established that albuminuria stems from disruptions in podocyte structure and function. Podocytes play a major role in the glomerular filtration barrier. The nephrin protein has been identified as a core component of the slit diaphragm in podocytes, and as such, the downregulation of nephrin expression has been described well in various proteinuric glomerulopathies, including DN. Previous studies have shown that the presence of urinary nephrin potentially signifies an early marker of podocyte injury in DN. More recently, there have been increasing bodies of evidence which suggest that circulating autoantibodies targeting nephrin contributes to the pathogenesis of podocytopathies. However, the functional significance of these circulating autoantibodies in patients with DN is not well understood. In this review, we aim to evaluate the significance of nephrin dysregulation in the pathogenesis of DN based on the current available literature and provide an overview on the application of circulating anti-nephrin autoantibodies in relation to its diagnostic as well as prognostic role in podocytopathies, including DN.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708012","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":"Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura.","authors":"Michael R Snyder, Robert W Maitta","doi":"10.3390/antib14010024","DOIUrl":"10.3390/antib14010024","url":null,"abstract":"<p><p>Autoantibodies to ADAMTS13 are at the center of pathology of the immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies are generated in response to foreign antigens, which can include infectious agents; however, these antibodies may at times cross-react with self-epitopes. This is one of the possible mechanisms mediating formation of anti-ADAMTS13 autoantibodies. The process known as \"antigenic mimicry\" may be responsible for the development of these autoantibodies that recognize and bind cryptic epitopes in ADAMTS13, disrupting its enzymatic function over ultra large von Willebrand factor multimers, forming the seeds for platelet activation and microthrombi formation. In particular, specific amino acid sequences in ADAMTS13 may lead to conformational structures recognized by autoantibodies. Generation of these antibodies may occur more frequently among patients with a genetic predisposition. Conformational changes in ADAMTS13 between open and closed states can also constitute the critical change driving either interactions with autoantibodies or their generation. Nowadays, there is a growing understanding of the role that autoantibodies play in ADAMTS13 pathology. This knowledge, especially of functional qualitative differences among antibodies and the ADAMTS13 sequence specificity of such antibodies, may make possible the development of targeted therapeutic agents to treat the disease. This review aims to present what is known of autoantibodies against ADAMTS13 and how their structure and function result in disease.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708278","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 Use of Heterologous Antigens for Biopanning Enables the Selection of Broadly Neutralizing Nanobodies Against SARS-CoV-2.","authors":"Vazirbek S Aripov, Anna V Zaykovskaya, Ludmila V Mechetina, Alexander M Najakshin, Alexander A Bondar, Sergey G Arkhipov, Egor A Mustaev, Margarita G Ilyina, Sophia S Borisevich, Alexander A Ilyichev, Valentina S Nesmeyanova, Anastasia A Isaeva, Ekaterina A Volosnikova, Dmitry N Shcherbakov, Natalia V Volkova","doi":"10.3390/antib14010023","DOIUrl":"10.3390/antib14010023","url":null,"abstract":"<p><p><b>Background:</b> Since the emergence of SARS-CoV-2 in the human population, the virus genome has undergone numerous mutations, enabling it to enhance transmissibility and evade acquired immunity. As a result of these mutations, most monoclonal neutralizing antibodies have lost their efficacy, as they are unable to neutralize new variants. Antibodies that neutralize a broad range of SARS-CoV-2 variants are of significant value in combating both current and potential future variants, making the identification and development of such antibodies an ongoing critical goal. This study discusses the strategy of using heterologous antigens in biopanning rounds. <b>Methods:</b> After four rounds of biopanning, nanobody variants were selected from a phage display library. Immunochemical methods were used to evaluate their specificity to the S protein of various SARS-CoV-2 variants, as well as to determine their competitive ability against ACE2. Viral neutralization activity was analyzed. A three-dimensional model of nanobody interaction with RBD was constructed. <b>Results:</b> Four nanobodies were obtained that specifically bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein and exhibit neutralizing activity against various SARS-CoV-2 strains. <b>Conclusions:</b> The study demonstrates that performing several rounds of biopanning with heterologous antigens allows the selection of nanobodies with a broad reactivity spectrum. However, the fourth round of biopanning does not lead to the identification of nanobodies with improved characteristics.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707994","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":"Treatment of Ebola Virus Disease: From Serotherapy to the Use of Monoclonal Antibodies.","authors":"Dmitriy N Shcherbakov, Anastasiya A Isaeva, Egor A Mustaev","doi":"10.3390/antib14010022","DOIUrl":"10.3390/antib14010022","url":null,"abstract":"<p><p>Ebola virus disease (EVD) is an acute illness with a high-case fatality rate (CFR) caused by an RNA virus belonging to the Filoviridae family. Over the past 50 years, regular EVD outbreaks have been reported. The West African EVD outbreak of 2013-2016 proved to be significantly more widespread and complex than previous ones, resulting in approximately 11,000 deaths. A coordinated international effort was required to bring the outbreak under control. One of the main challenges faced by clinicians and researchers combating EVD was the absence of vaccines and preventive treatments. Only recently have efforts led to the development of effective therapeutic options. Among these, monoclonal antibody-based drugs have emerged as the most promising agents for the urgent treatment of EVD. This article aims to review the key milestones in the development of antibody-based therapies for EVD, tracing the journey from the use of convalescent serum to the creation of effective monoclonal antibody-based drugs and their combinations.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708089","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":"Development of Fully Human Antibodies Targeting SIRPα and PLA2G7 for Cancer Therapy.","authors":"Seungmin Shin, Du-San Baek, John W Mellors, Dimiter S Dimitrov, Wei Li","doi":"10.3390/antib14010021","DOIUrl":"10.3390/antib14010021","url":null,"abstract":"<p><p><b>Background:</b> Macrophages play an important role in eliminating diseased and damaged cells through programmed cell death. Signal regulatory protein alpha (SIRPα) is a crucial immune checkpoint primarily expressed on myeloid cells and macrophages. It initiates a 'do not eat me' signal when engaged with CD47, which is typically expressed at elevated levels on multiple solid tumors. The phospholipase A2 Group 7 (PLA2G7), which is mainly secreted by macrophages, interacts with oxidized low-density lipoprotein (oxLDL) and associates with several vascular diseases and cancers. <b>Methods</b>: To identify potent fully human monoclonal antibodies (mAbs) against human SIRPα and PLA2G7, we conducted bio-panning of phage antibody libraries. <b>Results</b>: We isolated one human Fab (1B3) and VH (1A3) for SIRPα, as well as one human Fab (1H8) and one VH (1A9) for PLA2G7; the 1B3 Fab and 1A3 VH are competitively bound to SIRPα, interfering with CD47 binding. The 1B3 IgG and 1A3 VH-Fc augmented macrophage-mediated phagocytic activity when combined with the anti-EGFR antibody, cetuximab. The anti-PLA2G7 antibodies exhibited high specificity for the PLA2G7 antigen and effectively blocked the PLA2G7 enzymatic activity with half-maximal inhibitory concentrations (IC₅₀) in the single-digit nanomolar range. Additionally, 1H8 IgG and its derivative bispecific antibody exhibited the ability to block PLA2G7-mediated tumor cell migration. <b>Conclusions</b>: Our anti-SIRPα mAbs are expected to serve as potent and fully human immune checkpoint inhibitors of SIRPα, enhancing the antitumor responses of SIRPα-positive immune cells. Moreover, our anti-PLA2G7 mAbs represent promising fully human PLA2G7 enzymatic blockade antibodies with the potential to enhance both anti-tumor and anti-aging responses. Anti-SIRPα and PLA2G7 mAbs can modulate macrophage phagocytic activity and inflammatory responses against tumors.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708280","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":"Monoclonal Antibodies in Light of Mpox Outbreak: Current Research, Therapeutic Targets, and Animal Models.","authors":"Vladimir N Nikitin, Iuliia A Merkuleva, Dmitriy N Shcherbakov","doi":"10.3390/antib14010020","DOIUrl":"10.3390/antib14010020","url":null,"abstract":"<p><p>The rapid rise in monkeypox virus infections among humans from 2022 to 2024 has captured the attention of the global healthcare community. In light of the lack of mandatory vaccination and limited data on next-generation vaccines for monkeypox prevention, the urgent development of therapeutic agents has become a priority. One promising approach involves the use of neutralizing monoclonal antibodies. This review highlights significant advancements in the search for antibodies against human pathogenic orthopoxviruses, particularly focusing on their potential application against the monkeypox virus. We also analyze viral proteins that serve as targets for identifying therapeutic antibodies capable of neutralizing a wide range of viruses. Finally, we deemed it essential to address the challenges associated with selecting an animal model that can adequately reflect the infectious process of each orthopoxvirus species in humans.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708018","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":"IgE-Crosslinking-Induced Luciferase Expression Test as a Sensitive Indicator of <i>Anisakis</i> Allergy.","authors":"Haruyo Akiyama, Masashi Niwa, Chisato Kurisaka, Yuto Hamada, Yuma Fukutomi, Reiko Teshima","doi":"10.3390/antib14010019","DOIUrl":"10.3390/antib14010019","url":null,"abstract":"<p><p><b>Background:</b><i>Anisakis</i> allergy has been increasing, and the diagnosis of it is based on specific serum IgE detection. Recently, the IgE-crosslinking-induced luciferase expression (EXiLE) test has been proposed as convenient tool for detecting functionally specific IgE antibodies. Here, we investigated if the EXiLE test is a useful tool in the diagnosis of <i>Anisakis</i> allergy. <b>Methods:</b> HuRa-40 cells were sensitized using six serum types from three patients with <i>Anisakis</i> allergy at the time of the initial test and after 6-12 months. Thereafter, various concentrations of <i>Anisakis</i> worm protein (AWP) were reacted to measure the degree of EXiLE. The degree of EXiLE was compared with <i>Anisakis</i>-specific IgE antibody levels measured by the CAP-FEIA method, and the IgE-antibody-binding protein profile was examined using IgE immunoblotting. <b>Results:</b> The results showed a good correlation between the CAP-FEIA values and EXiLE obtained with 5 μg/mL of AWP (R = 0.91, <i>p</i> < 0.01), a strong response on IgE immunoblotting in the region containing proteins weighing ≥40,000 Da. In addition, after the onset of <i>Anisakis</i> allergy, the degree of serum EXiLE decreased in two patients whose <i>Anisakis</i>-specific IgE antibody levels decreased over time but increased in one patient whose specific IgE antibodies increased after repeated antigen sensitization. <b>Conclusions:</b> Based on these data, the AWP-induced EXiLE test seemed to be useful and convenient for the diagnosis of <i>Anisakis</i> allergy, supplementing specific IgE determinants. After allergy onset, the use of this method to observe changes in specific IgE levels over time may be important for predicting the risk of recurrence.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708284","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":"Avian Antibodies as Potential Therapeutic Tools.","authors":"Mats Eriksson, Anders Larsson","doi":"10.3390/antib14010018","DOIUrl":"10.3390/antib14010018","url":null,"abstract":"<p><p>Immunoglobulin Y (IgY) is the primary antibody found in the eggs of chicken (<i>Gallus domesticus</i>), allowing for large-scale antibody production with high titers, making them cost-effective antibody producers. IgY serves as a valuable alternative to mammalian antibodies typically used in immunodiagnostics and immunotherapy. Compared to mammalian antibodies, IgY offers several biochemical advantages, and its straightforward purification from egg yolk eliminates the need for invasive procedures like blood collection, reducing stress in animals. Due to the evolutionary differences between birds and mammals, chicken antibodies can bind to a broader range of epitopes on mammalian proteins than their mammalian counterparts. Studies have shown that chicken antibodies bind 3-5 times more effectively to rabbit IgG than swine antibodies, enhancing the signal in immunological assays. Additionally, IgY does not interact with rheumatoid factors or human anti-mouse IgG antibodies (HAMA), helping to minimize interference from these factors. IgY obtained from egg yolk of hens immunized against <i>Pseudomonas aeruginosa</i> has been used in patients suffering from cystic fibrosis and chronic pulmonary colonization with this bacterium. Furthermore, IgY has been used to counteract <i>streptococcus mutans</i> in the oral cavity and for the treatment of enteral infections in both humans and animals. However, the use of avian antibodies is limited to pulmonary, enteral, or topical application and should, due to immunogenicity, not be used for systemic administration. Thus, IgY expands the range of strategies available for combating pathogens in medicine, as a promising candidate both as an alternative to antibiotics and as a valuable tool in research and diagnostics.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466807","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":"Investigation of Antibody Pharmacokinetics in Male Reproductive System and Its Characterization Using a Translational PBPK Model.","authors":"Sree Ojili, Dhaval K Shah","doi":"10.3390/antib14010017","DOIUrl":"10.3390/antib14010017","url":null,"abstract":"<p><p><b>Objectives:</b> To investigate the pharmacokinetics (PK) of the monoclonal antibody (mAb) in male reproductive tissues and develop a translational physiologically based pharmacokinetic (PBPK) model to characterize the PK data. <b>Method:</b> The PK of a non-cross-reactive antibody (trastuzumab) was investigated in human FcRn-expressing male mice following a 10 mg/kg intravenous dose. The PK in plasma and male reproductive tissues (i.e., epididymis, testes, vas deferens, seminal vesicles, and prostate glands) were evaluated. The observed PK data in mice were mathematically characterized using a novel PBPK model for antibodies that contained male reproductive systems. The mouse PBPK model was scaled to rats, monkeys, and humans to predict the PK of antibodies in male reproductive organs across animal species. <b>Results</b>: Plasma and tissue PK data generated in mice suggest that antibody distribution in male reproductive tissues is generally lower compared to that of most of the organs. The antibody exposure in the testes was 1.70%, in the epididymis was 2.57%, in the vas deferens was 2.01%, in the seminal vesicle was 0.42%, and in the prostate gland was 0.52% of the plasma exposure. The plasma and tissue PK data were simultaneously characterized using the PBPK model, which incorporated the novel male reproductive system. All the predicted PK profiles were within two-fold of the observed data, as indicated by percentage prediction error (%PE) values. The mouse model was successfully translated to bigger animals, and the model was used to simulate the PK of antibodies in rat, monkey, and human male reproductive systems. <b>Conclusions</b>: The combination of the experimental data and novel PBPK model presented here provides unprecedented insights into the antibody distributions in different male reproductive tissues. The PBPK model can serve as a crucial tool for advancing the development of antibody-based therapies for treating sexually transmitted infections (STIs), cancers, and contraceptives.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466837","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}