ImmunoTargets and Therapy最新文献

{"title":"Pan-Cancer Analysis of the Prognostic and Immunotherapeutic Value of PDGFB.","authors":"Yuwei Bai, Xiaoyun Wang, Bei Wang","doi":"10.2147/ITT.S486609","DOIUrl":"10.2147/ITT.S486609","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer is a widespread epidemic that affects millions of individuals across the world. Identifying novel cancer targets is crucial to developing more effective cancer treatments. Platelet-derived growth factor-B (PDGFB) plays a critical role in various tumor processes, including angiogenesis and lymphatic metastasis. However, there is a lack of research on the role of PDGFB in these processes.</p><p><strong>Methods: </strong>To address this issue, we conducted a comprehensive analysis utilizing multiple online databases to investigate the expression, prognostic, tumor stemness, and immunological effect of PDGFB. In addition, clinical samples were validated using immunohistochemistry.</p><p><strong>Results: </strong>Our findings revealed that PDGFB was highly expressed in a diverse range of cancer types, and its expression and genetic modifications were significantly associated with clinical outcomes in certain tumors. In general, high expression of PDGFB in tumors is associated with poor prognosis. Surprisingly, PDGFB was found to be highly expressed in renal clear cell carcinoma but was associated with good prognosis. In contrast, PDGFB was low expressed in lung carcinoma, but its expression was found to improve patient survival. These findings demonstrate the complex role of PDGFB in different cancer types. The study also demonstrated that PDGFB was linked to RNA and DNA stemness in 15 and 36 tumor types, respectively, and had a positive association with tumor lymphocyte infiltration. Notably, PDGFB was found to be associated with immune modulators. PDGFB, which is involved in various immune responses, influences the malignant characteristics of various cancer types and controls immune cell infiltration. We confirmed that PDGFB positively correlated with CD8 and PDL1 expression in lower grade glioma.</p><p><strong>Conclusion: </strong>This study concludes that PDGFB may serve as a potential prognostic marker and a potential targetable pathway in cancer immunotherapy. Overall, the study sheds new light on the role of PDGFB in cancer and highlights its potential clinical significance.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"35-49"},"PeriodicalIF":6.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053708","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":"Increased Co-Expression of PD-L1 and CTLA-4 Predicts Poor Overall Survival in Patients with Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Cunte Chen, Kangjie Qiu, Jie Chen, Shunqing Wang, Yuping Zhang, Caixia Wang, Yangqiu Li","doi":"10.2147/ITT.S500723","DOIUrl":"10.2147/ITT.S500723","url":null,"abstract":"<p><strong>Purpose: </strong>Our previous study has demonstrated that high expression of immune checkpoints (ICs) was significantly associated with adverse clinical outcomes in patients with acute myeloid leukemia (AML). This study aims to investigate the significance of the alteration of IC co-expression for evaluating the prognosis of AML patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><strong>Patients and methods: </strong>Quantitative real-time PCR (qRT-PCR) data of bone marrow (BM) samples from 62 de novo AML patients, including 37 patients who received allo-HSCT and 25 patients who received chemotherapy only, were used for prognostic analysis.</p><p><strong>Results: </strong>High expression of PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 was associated with poor overall survival (OS) in AML patients receiving allo-HSCT, while the expression levels of PD-1, PD-L2, CTLA-4, and LAG-3, other than PD-L1, were not significantly correlated with OS in AML patients receiving chemotherapy. Importantly, PD-L1/CTLA-4 was the best combination model for predicting poor OS in AML patients following allo-HSCT, especially combined with minimal residual disease (MRD).</p><p><strong>Conclusion: </strong>High expression of ICs in BM of AML patients following allo-HSCT was related to poor outcomes, and increasing co-expression of PD-L1 and CTLA-4 might be one of the best immune biomarkers to predict outcomes in patients with AML.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"25-33"},"PeriodicalIF":6.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048041","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":"Targeting B and T Lymphocyte Attenuator Regulates Lupus Disease Development in NZB/W Mice.","authors":"Léa Gherardi, Lucie Aubergeon, Mélanie Sayah, Jean-Daniel Fauny, Hélène Dumortier, Fanny Monneaux","doi":"10.2147/ITT.S490573","DOIUrl":"10.2147/ITT.S490573","url":null,"abstract":"<p><strong>Purpose: </strong>The co-inhibitory receptor B and T Lymphocyte Attenuator (BTLA) negatively regulates B and T cell activation. We have previously shown an altered BTLA expression by regulatory T cells and an impaired capacity of BTLA to inhibit CD4⁺ T cell activation in lupus patients. In this study, we analyzed BTLA expression and function in the NZB/W lupus-mouse model and examined the therapeutic potential of BTLA targeting.</p><p><strong>Methods: </strong>BTLA expression and function were analyzed in young (10-12-week-old) and old-diseased NZB/W mice (>35-week-old with proteinuria) in comparison to age-related BALB/W control mice. 20-22 weeks old NZB/W mice (n=10) were injected i.p with 3 mg/kg, twice a week for ten weeks, with the anti-BTLA antibody 6F7 or its isotype control.</p><p><strong>Results: </strong>In old-diseased NZB/W mice, BTLA expression is slightly modified in B cell subsets whereas CD4⁺ T cells display impaired BTLA functionality. Administration of the 6F7 anti-BTLA antibody into 20-22 week-old NZB/W mice resulted in a delayed onset of proteinuria (p<0.01), limited kidney damages (p<0.05) and an increased survival rate (p<0.01) compared to isotype-treated mice. This beneficial effect was associated with a decrease in circulating B cell and spleen follicular B cell numbers. Regarding its mode of action, we demonstrated that the 6F7 antibody is not a depleting antibody and does not block HVEM binding to BTLA, but instead induces BTLA down modulation and exhibits in vivo agonist activity.</p><p><strong>Conclusion: </strong>Overall, our data confirm the involvement of BTLA in lupus pathogenesis and provide the first evidence that BTLA is a potential therapeutic target for the treatment of lupus.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"7-23"},"PeriodicalIF":6.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024958","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":"Daratumumab and Romiplostim Combined Therapy for a Long-Standing Refractory Primary Immune Thrombocytopenia - Case Report.","authors":"Ibrahim Zoubi, Amir Warwar, Shoshan Perek, Meir Preis","doi":"10.2147/ITT.S487895","DOIUrl":"10.2147/ITT.S487895","url":null,"abstract":"<p><p>Multi-refractory immune thrombocytopenia (ITP) is not uncommon and associated with high morbidity and mortality rates. Although the precise mechanism of ITP is not yet fully understood, a therapeutic approach that relies on using a single agent in each treatment line may not be sufficient in this population. We report the case of a 67-year-old female with long-standing multi-refractory ITP treated with a combination of Daratumumab and Romiplostim who achieved a durable response for more than 42 weeks. Owing to the presentation of chronic and refractory disease, we used a dual-agent approach to address early immune destruction and promote megakaryocyte platelet production. Three doses of Daratumumab were administered during the induction phase (weeks 0,1,5) and then at less frequent intervals - every 4-12 weeks for total of 4 doses during the maintenance phase. Romiplostim was administered weekly, with dose modification depending on the platelet count. We hypothesize that when combined with thrombopoietin receptor agonists (TPO-RAs), daratumumab administered at less frequent intervals over an extended period can be safely used, resulting in a prolonged response.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1-5"},"PeriodicalIF":6.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972404","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-GluK2 Encephalitis in an Asian Child: A Case Report and Literature Review.","authors":"Shimeng Chen, Miriam Kessi, Fang He, Fei Yin, Jing Peng, Lifen Yang","doi":"10.2147/ITT.S498345","DOIUrl":"10.2147/ITT.S498345","url":null,"abstract":"<p><strong>Background: </strong>Anti-glutamate kainate receptor subunit 2 (anti-GluK2) antibodies mediated encephalitis is very rare in both children and adults. This study aimed to describe the second report of the anti-GluK2 encephalitis worldwide, the first youngest patient worldwide, and the first case ever in Asia. Besides, this study provides a summary of the clinical manifestations of all previous reported cases.</p><p><strong>Methods: </strong>The patient was attended at the Department of Pediatrics, Xiangya Hospital, Central South University. Anti-GluK2 antibodies were tested in the serum and cerebrospinal fluid (CSF) by the indirect immunofluorescence on cell-based assays. The clinical information of the patient was collected. In addition, a literature search was carried out in the PubMed.</p><p><strong>Results: </strong>Our patient was a male who presented with lethargy, recurrent dizziness and vomiting, headache and cerebellar ataxia at the age of 13 years. Prodromal illnesses included Herpes Zoster infection and Mycoplasma pneumonia. The anti-GluK2 antibodies and elevated IL-6 levels were detected in serum while high oligoclonal bands levels were found in the CSF. The intravenous methylprednisolone, immunoglobulin, antibiotics and other symptomatic treatments helped the patient to recover full. We could only find one previous report in the literature (from Barcelona). The literature review plus our report unveiled eight patients with pure anti-GluK2 antibodies related encephalitis. The median age of onset was 28.50 years and majority were males (75.00%). Most of the cases (87.50%) presented with acute cerebellitis symptoms and signs. Preceding or concurrent infection was observed in two patients, while paraneoplastic tumors were observed in two patients. Patients had non-parenchymal brain lesions; the commonest anomalies were those localized in the cerebellum (62.50%).</p><p><strong>Conclusion: </strong>Our report provides more evidence that anti-GluK2 antibodies may be pathogenic for the autoimmune encephalitis (cerebellitis). Immunotherapy can be used to treat it with good outcome.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"805-811"},"PeriodicalIF":6.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883123","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":"Lipopolysaccharide in Bile Promotes the Neutrophil Extracellular Traps-Induced Gallstone Formation by Activating the Gallbladder Immune Barrier.","authors":"Jingjing Yu, Ziang Meng, Xuxu Liu, Yi Zheng, Dongbo Xue, Chenjun Hao, Liyi Wang","doi":"10.2147/ITT.S495095","DOIUrl":"10.2147/ITT.S495095","url":null,"abstract":"<p><strong>Background: </strong>Cholelithiasis areis a common digestive system disorder, with cholesterol gallstones being the most prevalent type. Gallstones lead to many severe complications, posing a significant burden on global healthcare systems. Many studies have shown associations between biliary microbiota, gallbladder immune microenvironment, and gallstone formation. However, the specific immune mechanisms underlying the cholesterol gallstone formation have not been fully elucidated.</p><p><strong>Methods: </strong>In this study, gallbladderand bile samples from 8 asymptomatic patients with cholelithiasis undergoing cholecystectomy and 11 healthy liver transplant donors were collected for tissue transcriptome sequencing and differential analysis. Male C57BL/6J mice were fed a normal or lithogenic diet for 6 weeks. Starting from the third week, lipopolysaccharide (LPS) or specific regulators were injected intraperitoneally once a week for a total of 3 times. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were employed for quantitative, qualitative or localization analysis of LPS, neutrophil extracellular traps (NETs), inflammatory factors, proteins, and mRNAs using samples collected from mice.</p><p><strong>Results: </strong>In patients with cholelithiasis, the gallbladder mechanical barrier is impaired, resulting in an immune-activated state. LPS induces damage to the gallbladder mucosal mechanical barrier through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, it stimulates the continuous production of NETs through the TLR4/Phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, aggravating the formation of gallstones.</p><p><strong>Conclusion: </strong>With the biliary dysbiosis, excessive LPS can invade the submucosa of the gallbladder, leading to chronic inflammation that recruits neutrophils to form NETs, which are ultimately expelled into bile, thereby promoting the formation of gallstones.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"789-803"},"PeriodicalIF":6.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877878","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":"NLRP3 Inflammasome Upregulates PD-L1 in Ovarian Cancer and Contributes to an Immunosuppressive Microenvironment.","authors":"Wenjing Pan, Zhaoyang Jia, Jingtong Du, Kexin Chang, Yiming Liu, Wei Liu, Xibo Zhao, Wenhua Tan","doi":"10.2147/ITT.S495564","DOIUrl":"10.2147/ITT.S495564","url":null,"abstract":"<p><strong>Introduction: </strong>The NLRP3 inflammasome has been implicated in the initiation of inflammation and tumorigenesis; however, its role in epithelial ovarian cancer (EOC) remains unclear.</p><p><strong>Methods: </strong>This study employed high-throughput sequencing data, ELISA, clone formation assay, Western blot, and flow cytometric analysis to investigate the specific role of the NLRP3 inflammasome in EOC.</p><p><strong>Results: </strong>NLRP3 was highly expressed in human EOC tissues and correlated with an unfavorable prognosis. Activation of the NLRP3 inflammasome by LPS and ATP promoted EOC cell proliferation and increased IL-1 and PD-L1 levels. MCC950, a NLRP3 inflammasome blocker, reduced IL-1 and PD-L1 levels and diminished tumor-immune suppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and PD-1⁺ CD4⁺ T cells, in a murine model of ovarian cancer. This intervention also suppressed tumor growth.</p><p><strong>Conclusion: </strong>Our investigation revealed the pro-tumorigenic role of the NLRP3 inflammasome and its regulation of PD-L1 expression in EOC. Blockade of the NLRP3 inflammasome led to reduced PD-L1 expression, fewer immunosuppressive cells, and suppressed tumor growth. These findings suggest that targeting the NLRP3 inflammasome-PD-L1 axis could be a novel treatment approach for ovarian cancer.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"775-788"},"PeriodicalIF":6.2,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865649","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":"Microbiome Differences in Colorectal Cancer Patients and Healthy Individuals: Implications for Vaccine Antigen Discovery.","authors":"Gordon C Ibeanu, Adekunle B Rowaiye, Joy C Okoli, Daniel U Eze","doi":"10.2147/ITT.S486731","DOIUrl":"10.2147/ITT.S486731","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with numerous risk factors contributing to its development. Recent research has illuminated the significant role of the gut microbiota in CRC pathogenesis, identifying various microbial antigens as potential targets for vaccine development.</p><p><strong>Aim: </strong>This review aimed at exploring the potential sources of microbial antigens that could be harnessed to create effective CRC vaccines and understand the role of microbiome-CRC interactions in carcinogenesis.</p><p><strong>Methods: </strong>A comprehensive search of original research and review articles on the pathological links between key microbial candidates, particularly those more prevalent in CRC tissues, was conducted. This involved extensive use of the PubMed and Medline databases, as well as the Google Scholar search engine, utilizing pertinent keywords. A total of one hundred and forty-three relevant articles in English, mostly published between 2018 and 2024, were selected.</p><p><strong>Results: </strong>Numerous microbes, particularly bacteria and viruses, are significantly overrepresented in CRC tissues and have been shown to promote tumorigenesis by inducing inflammation and modulating the immune system. This makes them promising candidates for antigens in the development of CRC vaccines.</p><p><strong>Conclusion: </strong>The selection of microbial antigens focuses on their capacity to trigger a strong immune response and their link to tumor presence and progression. Identifying and validating these antigens through preclinical testing is essential in developing a CRC vaccine.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"749-774"},"PeriodicalIF":6.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855721","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":"TRPC6 is a Biomarker for Prognosis and Immunotherapy of Stomach Adenocarcinoma Based on Bioinformatic Analysis and Experimental Validation.","authors":"Xingchi Hu, Hongwei Wang, Haitao Sun, Jingxin Zhang, ZhenXiong Ye, Zhenhua Huang","doi":"10.2147/ITT.S488953","DOIUrl":"10.2147/ITT.S488953","url":null,"abstract":"<p><strong>Background: </strong>Transient receptor potential canonical 6 (TRPC6), a key member of the TRPC family, is involved in diverse physiological and pathological processes. Although previous studies have implicated TRPC6 in the progression of stomach adenocarcinoma (STAD), its precise functions and mechanisms remain unclear. Understanding TRPC6's role in STAD may provide insights into its prognostic and therapeutic potential.</p><p><strong>Methods: </strong>Using transcriptional and clinical data from The Cancer Genome Atlas (TCGA) database, we assessed the expression and prognostic value of TRPC6 in STAD through Kaplan-Meier survival curve analysis and correlation studies. Immune-related parameters, including immune cell infiltration and immune checkpoint gene expression, were also evaluated. Additionally, drug response analyses explored TRPC6's association with therapeutic agents. In vitro experiments were conducted to investigate TRPC6's role in STAD cell proliferation, migration, and invasion, focusing on its regulation of the PI3K-Akt signaling pathway.</p><p><strong>Results: </strong>TRPC6 was significantly overexpressed in STAD tissues compared to normal tissues, with high TRPC6 expression associated with poor overall survival. TRPC6 expression correlated strongly with immune cell infiltration, immune checkpoint genes, and sensitivity to therapies such as Lapatinib, anti-CTLA4, and anti-PD1 treatments. Functional assays confirmed that TRPC6 promotes STAD cell proliferation, migration, and invasion by activating the PI3K-Akt signaling pathway.</p><p><strong>Conclusion: </strong>This study highlights the prognostic significance of TRPC6 in STAD and its potential as a therapeutic target. TRPC6's involvement in immune regulation and cancer cell progression underscores its dual role in STAD pathogenesis and treatment, offering new avenues for targeted therapy development.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"735-748"},"PeriodicalIF":6.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847706","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":"Advances in B Cell Targeting for Treating Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis.","authors":"Guanlian Hu, Xue Zhao, Yiren Wang, Xiaoyan Zhu, Zhan Sun, Xiaoxiao Yu, Jiahui Wang, Qian Liu, Jing Zhang, Yingna Zhang, Junhong Yang, Ting Chang, Zhe Ruan, Jie Lv, Feng Gao","doi":"10.2147/ITT.S492062","DOIUrl":"10.2147/ITT.S492062","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is a typical autoimmune disease of the nervous system. It is characterized by skeletal muscle weakness and fatigue due to impaired neuromuscular junction transmission mediated by IgG autoantibodies. Muscle-specific receptor tyrosine kinase-associated MG (MuSK-MG), a rare and severe subtype of MG, is distinguished by the presence of anti-MuSK antibodies; it responds poorly to traditional therapies. Recent research on MuSK-MG treatment has focused on specific targeted therapies. Since B cells play a critical pathogenic role in producing autoantibodies and inflammatory mediators, they are often considered the preferred target for treating MuSK-MG. Currently, various B cell-targeted drugs have been developed to treat MuSK-MG; they have shown good therapeutic effects. This review explores the evolving landscape of B cell-targeted therapies in MuSK-MG, focusing on their mechanisms, efficacy, and safety, and the current limitations associated with their use. We discuss current B cell-targeted therapies aimed at depleting or modulating B cells via both direct and indirect approaches. Furthermore, we focus on novel and promising strategies such as Chimeric Autoantibody Receptor T cell therapy, which explicitly targets MuSK-specific B cells without compromising general humoral immunity. Finally, this review provides an outlook on the potential benefits and limitations of B cell-targeted therapy in developing new therapies for MuSK-MG. We conclude by discussing future research efforts needed to optimize these therapies, expand treatment options, and improve long-term outcomes in MuSK-MG management.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"707-720"},"PeriodicalIF":6.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829957","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}