Antibodies最新文献

{"title":"T330M Substitution in the Sodium-Dependent Phosphate Transporter NaPi2b Abolishes the Efficacy of Monoclonal Antibodies Against MX35 Epitope.","authors":"Leisan F Bulatova, Vera S Skripova, Aisylu R Sagdeeva, Ramilia A Vlasenkova, Tatiana A Bugaenko, Rezeda R Galimova, Alfiya I Nesterova, Yuliya V Filina, Ramziya G Kiyamova","doi":"10.3390/antib14020030","DOIUrl":"https://doi.org/10.3390/antib14020030","url":null,"abstract":"<p><p><b>Background:</b> Monoclonal antibodies against the sodium-dependent phosphate transporter NaPi2b (<i>SLC34A2</i>) represent a promising approach in the treatment of ovarian and lung cancer. Of particular interest is the potential cancer-specific MX35 epitope of NaPi2b, as it serves as a target for monoclonal antibodies studied at various stages of preclinical and clinical trials. However, variations in the NaPi2b protein structure may limit the efficacy of therapeutic antibodies by affecting the accessibility of the MX35 epitope. <b>Methods:</b> An in silico analysis was performed using data from 101,562 tumor samples. Genomic DNA sequencing was conducted on blood samples from patients with ovarian carcinoma, breast cancer, and renal carcinoma to access the frequency of germline mutations in the <i>SLC34A2</i> gene region encoding the MX35 epitope. To assess the impact of the selected mutation, we generated a model cell line through site-directed mutagenesis carrying the mutant NaPi2b variant. <b>Results:</b> Using in silico analysis, we identified 17 unique variants in the <i>SLC34A2</i> gene leading to amino acid substitutions within the MX35 epitope of the NaPi2b. Among these, the most prevalent mutation, c.989C>T, resulting in p.T330M substitution, was detected in 5 out of 64 patients through genomic DNA sequencing. Using site-directed mutagenesis, we created the OVCAR-8/NaPi2b^p.T330M model cell line. L3 (28/1) monoclonal antibodies specific to the MX35 epitope failed to recognize the mutant NaPi2b^p.T330M variant compared to the wild-type of the NaPi2b in both Western blot and confocal microscopy experiments. <b>Conclusions:</b> The obtained data may serve as a basis for predicting the efficacy of monoclonal antibody-based targeted therapy binding to the MX35 epitope of NaPi2b in the treatment of oncological diseases.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952579","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 Novel Method for Preparing Uniform Micro-Sized Dry Powder Formulations, Including Aggregation-Controlled VHH.","authors":"Tatsuru Moritani, Hidekazu Masaki, Ryo Yonehara, Takeru Suzuki, Hidenao Arai, Masayuki Tsuchiya, Naoto Nemoto","doi":"10.3390/antib14020029","DOIUrl":"https://doi.org/10.3390/antib14020029","url":null,"abstract":"<p><strong>Background: </strong>The preparation of antibodies in powder form without changing their physicochemical properties may enable their use in new drug delivery system therapies or non-refrigerated storage. The variable domain of heavy-chain antibodies (VHHs) is more suited for this purpose than that of conventional antibodies because of VHHs' high thermal stability and ability to refold.</p><p><strong>Methods: </strong>In this report, the fine droplet drying (FDD) process was selected as the powderization technique because of its favorable features, such as mild drying conditions and the generation of uniform particle sizes. The aggregation, binding, particle, and in vitro inhalation properties of the prepared VHH powders (VHHps) were evaluated.</p><p><strong>Results: </strong>The amount of aggregated VHHs present in the VHHps depended on the flow temperature during the FDD process, with higher temperatures yielding a higher aggregation ratio. In contrast, no significant difference in binding activity was observed between each VHHp preparation and the native VHHs. However, this process degraded VHHs or inactivated their function, and ultimately, only about 30% of the original VHHs were functional, whereas the remaining VHHs that were not degraded showed little loss of functionality, even after storage at room temperature for more than two years. Analysis of the VHHp samples revealed that the particles were uniformly spherical with a single-micron size. The VHHps showed fine inhalation properties in the inhalation property test.</p><p><strong>Conclusions: </strong>These findings suggest that the FDD process affords various VHH powder formulations, including pharmaceutical formulations.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062053","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":"Discovery of Antibodies Against Endemic Coronaviruses with NGS-Based Human Fab Phage Display Platform.","authors":"Oscar Chi-Chien Pan, Sean Miller, Ruchin Patel, Shreya Mukhopadhyay, Giancarlo Sarullo, Gwenny Go, Jennifer Galli, Jamie Hessels, Barbara Schlingmann-Molina, Emmanuel Ndashimye, Zhiyun Wen, Christopher Warren, Eberhard Durr, Lan Zhang, Kalpit A Vora, Arthur Fridman, Zhifeng Chen","doi":"10.3390/antib14020028","DOIUrl":"https://doi.org/10.3390/antib14020028","url":null,"abstract":"<p><p><b>Background:</b> There is an unmet medical need to develop a vaccine targeting endemic coronaviruses. Antigen-specific monoclonal antibodies (mAbs) are crucial for many assays to support vaccine development. <b>Objective:</b> In this study, we used the HuCal Fab phage display library with a diversity of 4.5 × 10¹⁰ to identify antibodies specific to the spike proteins of the four endemic coronaviruses: OC43, NL63, 229E, and HKU1. <b>Methods:</b> As proof of concept, we established a newly designed platform using a long-read NGS workflow for antibody discovery and compared the results against the traditional workflow using Sanger sequencing consisting of lengthy and laborious benchwork. <b>Results:</b> The long-read NGS workflow identified most of the antibodies seen from the Sanger sequencing workflow, and many more additional antigen-specific antibodies against the endemic coronaviruses. Overall efficiency improved up to three times, comparing the traditional workflow with the NGS workflow. Of the 113 NGS-derived mAbs isolated to bind the four endemic coronavirus spike proteins, 107/113 (94.7%) had potent ELISA binding affinities (EC50 < 150 ng/mL, or <1 nM), and 61/113 (54%) had extremely potent ELISA binding affinities (EC50 of <15 ng/mL, or <0.1 nM). <b>Conclusions:</b> We successfully developed and incorporated the long-read NGS workflow to generate target-specific antibodies with many antibodies at sub-nanomolar affinities that are likely missed by a traditional workflow. We identified strong neutralizing antibodies, proving that our endemic spike proteins are capable of generating antibodies that could offer protection against the endemic HCoVs.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964312","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":"Low Serological Agreement of Hepatitis E in Immunocompromised Cancer Patients: A Comparative Study of Three Anti-HEV Assays.","authors":"Isabel-Elena Haller, Mark Reinwald, Janine Kah, Franz A M Eggert, Sandra Schwarzlose-Schwarck, Kristoph Jahnke, Stefan Lüth, Werner Dammermann","doi":"10.3390/antib14020027","DOIUrl":"https://doi.org/10.3390/antib14020027","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hepatitis E virus (HEV) is one of the leading causes of acute hepatitis, with immunosuppressed individuals, such as oncology patients, being particularly vulnerable to chronic infections that may progress to liver disease or fatal outcomes. Assay variability complicates HEV prevalence assessment in at-risk groups. This study aimed to compare the reliability and concordance of three HEV antibody assays-Wantai, Euroimmun, and Elecsys^®-in immunosuppressed oncology patients.</p><p><strong>Methods: </strong>In this prospective pilot study, serum samples were obtained from oncology patients between September 2020 and October 2021. Samples were collected both at baseline (treatment-naive) and during ongoing treatment. A healthy control group was retrospectively included for comparative analysis. Anti-HEV IgM and IgG antibodies were tested in all samples using enzyme-linked immunosorbent assays (Wantai, Euroimmun) and an electrochemiluminescence immunoassay (Elecsys^®). Demographic and clinical data, along with information on HEV risk factors, were extracted from medical records and patient questionnaires.</p><p><strong>Results: </strong>HEV IgM prevalence ranged from 0% (Wantai) to 6% (Elecsys^®), while IgG prevalence was 12% (Euroimmun), 38% (Wantai), and 53% (Elecsys^®). Concordance was poor, with Cohen's Kappa values indicating slight to moderate agreement (κ = 0.000-0.553). Patients with hematological malignancies exhibited the highest IgG seroprevalence. Risk factor analysis revealed the highest association between HEV exposure and the consumption of undercooked pork or crop-based agriculture.</p><p><strong>Conclusions: </strong>Significant variability among HEV serological assays highlights the challenges of reliable HEV diagnostics in immunosuppressed oncology patients. Assay selection and improved testing strategies are critical for this high-risk group.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"14 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960424","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":"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}