BioDrugs最新文献

{"title":"In Vitro Biological Characterization of Recombinant Insulin Aspart from Biogenomics and Originator Insulin Aspart.","authors":"Akshay G Mishra,&nbsp;Rutuja B Deshmane,&nbsp;Damodar K Thappa,&nbsp;Jeseena Lona,&nbsp;Nikhil S Ghade,&nbsp;Sanjay M Sonar,&nbsp;Archana R Krishnan","doi":"10.1007/s40259-023-00607-4","DOIUrl":"https://doi.org/10.1007/s40259-023-00607-4","url":null,"abstract":"<p><strong>Background: </strong>Bioassays are used to identify the pharmacological activity of new or chemically unknown compounds, as well as their undesirable effect, including toxicity. Biological assays are also required to ensure the quality, safety, and efficacy of recombinant biologics to confirm its biosimilarity to its originator. In the present study, analytical similarity between the biosimilar and its innovator is established by in vitro bioassays.</p><p><strong>Objective: </strong>The objective of this study was to show the comparative in vitro characterization of the recombinant insulin aspart from BioGenomics with its originator insulin aspart, using relevant biological assays.</p><p><strong>Methods: </strong>In vitro assays such as receptor binding, receptor autophosphorylation, glucose uptake, and mitogenic potential were analyzed for biological characterization of BioGenomics recombinant insulin aspart (BGL-ASP) manufactured by BioGenomics Limited and NovoRapid^® as the reference medicinal product (RMP) manufactured by Novo Nordisk. Insulin receptor binding was studied by a state-of-the-art method, surface plasmon resonance (SPR) for biomolecular interactions. The receptor autophosphorylation assay measures the phosphorylated insulin receptor in cell lysates. The glucose uptake assay measures the uptake of glucose by 3T3-L1 cells in the presence of insulin. Lipogenesis was studied in treated 3T3-L1 cells by detecting the accumulation of lipid droplets in the cells. Mitogenic effect was studied by cell proliferation assay using MCF-7 cells. A rabbit bioidentity test was performed by measuring the sudden decrease in blood glucose in the presence of insulin.</p><p><strong>Results: </strong>The binding studies showed that the affinity of BGL-ASP was highly comparable to NovoRapid^®. Insulin receptor autophosphorylation, glucose uptake, and lipogenesis demonstrated high similarity to the RMP. The mitogenic assay for BGL-ASP did not show any proliferative effect and was comparable to the RMP. The in vivo bioidentity test showed that the BGL-ASP is highly similar to the innovator, NovoRapid^®.</p><p><strong>Conclusion: </strong>The biological characterization studies of BGL-ASP demonstrated high binding and functional similarity to NovoRapid^®.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"709-719"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Gene Therapy as a Potential Paradigm Shift in Treating Severe Hemophilia.","authors":"Courtney D Thornburg,&nbsp;Dana H Simmons,&nbsp;Annette von Drygalski","doi":"10.1007/s40259-023-00615-4","DOIUrl":"https://doi.org/10.1007/s40259-023-00615-4","url":null,"abstract":"<p><p>Hemophilia is characterized by a deficiency in coagulation factors VIII or IX. The general standard of care for severe hemophilia is frequent intravenous recombinant or plasma-derived factor replacement to prevent bleeding. While this treatment is effective in preventing bleeding, frequent infusions are burdensome for patients. Nonadherence to the therapeutic regimen leaves people with hemophilia at risk for spontaneous and traumatic bleeds into joints as well as life-threatening bleeds such as intracranial hemorrhage. The chronicity of the disorder often leads to the formation of target joints, causing long-term pain and impairing mobility. As a monogenic disorder with well-understood genetics, hemophilia is an ideal disorder for implementing innovations in gene therapies. Indeed, recent approvals of two gene therapy products have the potential to shift the hemophilia treatment paradigm. Valoctocogene roxaparvovec and etranacogene dezaparvovec-drlb are gene therapies for hemophilia A and B, respectively. These therapies, given as a single intravenous infusion, may improve patients' quality of life, decreasing treatment burden and resulting in factor expression that virtually eliminates the need for factor replacement. Since both treatments involve viral vectors targeted to the liver, short- and long-term safety and efficacy monitoring involves monitoring liver enzymes to track liver health. Long-term monitoring of efficacy, durability of gene expression, and safety are ongoing. Gene therapy presents a promising new therapeutic option for patients with hemophilia and warrants continued innovation and investigation.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"595-606"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/6f/40259_2023_Article_615.PMC10432364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Going Beyond Host Defence Peptides: Horizons of Chemically Engineered Peptides for Multidrug-Resistant Bacteria.","authors":"Bernardo Cavallazzi Sebold,&nbsp;Junjie Li,&nbsp;Guoying Ni,&nbsp;Quanlan Fu,&nbsp;Hejie Li,&nbsp;Xiaosong Liu,&nbsp;Tianfang Wang","doi":"10.1007/s40259-023-00608-3","DOIUrl":"https://doi.org/10.1007/s40259-023-00608-3","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) bacteria are considered a health threat worldwide, and this problem is set to increase over the decades. The ESKAPE, a group of six pathogens including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. is the major source of concern due to their high death incidence and nosocomial acquired infection. Host defence peptides (HDPs) are a class of ribosomally synthesised peptides that have shown promising results in combating MDR, including the ESKAPE group, in- and outside bacterial biofilms. However, their poor pharmacokinetics in physiological mediums may impede HDPs from becoming viable clinical candidates. To circumvent this problem, chemical engineering of HDPs has been seen as an emergent approach to not only improve their pharmacokinetics but also their efficacy against pathogens. In this review, we explore several chemical modifications of HDPs that have shown promising results, especially against ESKAPE pathogens, and provide an overview of the current findings with respect to each modification.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"607-623"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/2a/40259_2023_Article_608.PMC10432368.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I, Randomized, Placebo-Controlled, Dose-Escalation Study of GB223, a Fully-Humanized Monoclonal Antibody to RANKL, in Healthy Chinese Adults.","authors":"Chen Li,&nbsp;Haiyan Liu,&nbsp;Yixiang Liao,&nbsp;Yu Zhu,&nbsp;Jingyuan Tian,&nbsp;Xuan Wang,&nbsp;Zhiqin Hu,&nbsp;Yaoxuan Zhan,&nbsp;Xianbo Li,&nbsp;Xintong Liang,&nbsp;Jin He,&nbsp;Yongmei Li,&nbsp;Dewei Shang,&nbsp;Qingshan Zheng,&nbsp;Tenghua Wang,&nbsp;Haifeng Song,&nbsp;Yi Fang","doi":"10.1007/s40259-023-00604-7","DOIUrl":"https://doi.org/10.1007/s40259-023-00604-7","url":null,"abstract":"<p><strong>Background: </strong>GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated.</p><p><strong>Patients and methods: </strong>This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140-252 days.</p><p><strong>Results: </strong>The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (T_max) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis-Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h^-1) and females (0.0081 h^-1). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42-168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1%), blood phosphorus decreased (67.6%) and blood calcium decreased (58.8%). In the GB223 group, 44.1% (15/34) of subjects were antidrug antibody positive after dosing.</p><p><strong>Conclusion: </strong>In this study, we demonstrated for the first time that a single subcutaneous injection of GB223, from 7 to 140 mg, is safe and well tolerated in healthy Chinese subjects. GB223 has a nonlinear pharmacokinetic profile, and sex was a potential covariate that may affect the absorption rate of GB223.</p><p><strong>Clinical trial registration: </strong>NCT04178044 and ChiCTR1800020338.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"721-735"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home-Based Infusion of Alglucosidase Alfa Can Safely be Implemented in Adults with Late-Onset Pompe Disease: Lessons Learned from 18,380 Infusions.","authors":"Imke A M Ditters,&nbsp;Harmke A van Kooten,&nbsp;Nadine A M E van der Beek,&nbsp;Jacqueline F Hardon,&nbsp;Gamida Ismailova,&nbsp;Esther Brusse,&nbsp;Michelle E Kruijshaar,&nbsp;Ans T van der Ploeg,&nbsp;Johanna M P van den Hout,&nbsp;Hidde H Huidekoper","doi":"10.1007/s40259-023-00609-2","DOIUrl":"https://doi.org/10.1007/s40259-023-00609-2","url":null,"abstract":"<p><strong>Background: </strong>Enzyme replacement therapy (ERT) with alglucosidase alfa is the treatment for patients with Pompe disease, a hereditary metabolic myopathy. Home-based ERT is unavailable in many countries because of the boxed warning alglucosidase alfa received due to the risk of infusion-associated reactions (IARs). Since 2008, home infusions have been provided in The Netherlands.</p><p><strong>Objectives: </strong>This study aimed to provide an overview of our experience with home-based infusions with alglucosidase alfa in adult Pompe patients, focusing on safety, including management of IARs.</p><p><strong>Method: </strong>We analysed infusion data and IARs from adult patients starting ERT between 1999 and 2018. ERT was initially given in the hospital during the first year. Patients were eligible for home treatment if they were without IARs for multiple consecutive infusions and if a trained home nurse, with on-call back-up by a doctor, was available. The healthcare providers graded IARs.</p><p><strong>Results: </strong>We analysed data on 18,380 infusions with alglucosidase alfa in 121 adult patients; 4961 infusions (27.0%) were given in hospital and 13,419 (73.0%) were given at home. IARs occurred in 144 (2.9%) hospital infusions and 113 (0.8%) home infusions; 115 (79.9% of 144) IARs in hospital and 104 (92.0% of 113) IARs at home were mild, 25 IARs (17.4%) in hospital and 8 IARs (7.1%) at home were moderate, and very few severe IARs occurred (4 IARs in hospital [2.8%] and 1 IAR at home [0.9%]). Only one IAR in the home situation required immediate clinical evaluation in the hospital.</p><p><strong>Conclusion: </strong>Given the small numbers of IARs that occurred with the home infusions, of which only one was severe, we conclude that alglucosidase alfa can be administered safely in the home situation, provided the appropriate infrastructure is present.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 5","pages":"685-698"},"PeriodicalIF":6.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/12/40259_2023_Article_609.PMC10432339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10380486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-Drug Conjugates in the Treatment of Urothelial Cancer.","authors":"Avani M Singh,&nbsp;Jose A Guevara-Patino,&nbsp;Xuefeng Wang,&nbsp;Roger Li,&nbsp;Guru Sonpavde,&nbsp;Rohit K Jain","doi":"10.1007/s40259-023-00606-5","DOIUrl":"https://doi.org/10.1007/s40259-023-00606-5","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have transformed the treatment landscape in oncology and become an essential therapeutic modality. In urothelial carcinoma (UC), the two ADCs that have been especially successful in clinical practice are enfortumab vedotin and sacituzumab govitecan. These drugs are currently approved as monotherapy for later lines of treatment in locally advanced or metastatic UC and have had a significant impact for patients with limited treatment options. Combinational trials, as well as additional ADCs, are currently being investigated in the treatment of UC for subsequent lines of therapy as overall survival rates remain dismal.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 4","pages":"505-520"},"PeriodicalIF":6.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Interchangeability of AVT02 and Humira^® in Participants with Moderate‑to‑Severe Chronic Plaque Psoriasis: Pharmacokinetics, Efficacy, Safety, and Immunogenicity Results from a Multicenter, Double-Blind, Randomized, Parallel-Group Study.","authors":"Steven R Feldman,&nbsp;Richard Kay,&nbsp;Nataliya Reznichenko,&nbsp;Joanna Sobierska,&nbsp;Roshan Dias,&nbsp;Hendrik Otto,&nbsp;Halimu N Haliduola,&nbsp;Abid Sattar,&nbsp;Ruth Ruffieux,&nbsp;Heimo Stroissnig,&nbsp;Fausto Berti","doi":"10.1007/s40259-023-00600-x","DOIUrl":"https://doi.org/10.1007/s40259-023-00600-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The US Food and Drug Administration (FDA) interchangeability guidelines state that the primary endpoint in a switching study should assess the impact of switching between the proposed interchangeable product and the reference product on clinical pharmacokinetics (PK) and pharmacodynamics (if available), as these assessments are generally sensitive to changes in immunogenicity and/or exposure that may arise due to switching. In addition, interchangeability designation requires no clinically meaningful difference in safety and efficacy of switching between the biosimilar and reference, compared with when using the reference product alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt; The aim of this study was to investigate the PK, immunogenicity, efficacy, and safety in participants undergoing repeated switches between Humira&lt;sup&gt;®&lt;/sup&gt; and AVT02 as part of a global interchangeable development program.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter, randomized, double-blind, parallel-group study in patients with moderate-to-severe plaque psoriasis comprises three parts: lead-in period (weeks 1-12), switching module (weeks 12-28), and the optional extension phase (weeks 28-52). Following the lead-in period during which all participants received the reference product (80 mg in week 1, followed by 40 mg every other week), participants with a clinical response of ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI75) were randomized 1:1 to receive AVT02 alternating with the reference product (switching arm) or reference product only (non-switching arm). At week 28, participants who were PASI50 responders could opt to take part in an open-label extension phase receiving AVT02 up to week 50, with an end of study visit at week 52. PK, safety, immunogenicity, and efficacy were evaluated at various timepoints throughout the study for both switching and non-switching arms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 550 participants were randomized to switching (277) and non-switching arms (273). The switching versus non-switching arithmetic least square means ratio [90% confidence intervals (CIs)] was 101.7% (91.4-112.0%) for the area under the concentration-time curve over the dosing interval from weeks 26-28 (AUC&lt;sub&gt;tau, W26-28&lt;/sub&gt;) and 108.1% (98.3-117.9%) for maximum concentration over the dosing interval from weeks 26-28 (C&lt;sub&gt;max, W26-28&lt;/sub&gt;). The 90% CIs for the switching versus non-switching arithmetic means ratio for primary endpoints AUC&lt;sub&gt;tau, W26-28&lt;/sub&gt; and C&lt;sub&gt;max, W26-28&lt;/sub&gt; were within the prespecified limits of 80-125%, demonstrating comparable PK profiles between groups. In addition, the PASI, Dermatology Life Quality Index, and static Physician's Global Assessment efficacy scores were highly similar for both treatment groups. There were no clinically meaningful differences between the immunogenicity and safety assessments of repeated switching between AVT02 and the reference product, versu","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 4","pages":"551-567"},"PeriodicalIF":6.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/8c/40259_2023_Article_600.PMC10197027.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization for the Similarity Assessment between Proposed Biosimilar SB12 and Eculizumab Reference Product Using a State-of-the-Art Analytical Method.","authors":"Hyunsoo Kim,&nbsp;Eunkyoung Hong,&nbsp;Jungmin Lee,&nbsp;Seokku Hong,&nbsp;Jihye Kim,&nbsp;Miju Cho,&nbsp;Yikwon Kim,&nbsp;Taekyung Yoo","doi":"10.1007/s40259-023-00591-9","DOIUrl":"https://doi.org/10.1007/s40259-023-00591-9","url":null,"abstract":"<p><strong>Background: </strong>SB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, and neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 antibody-positive.</p><p><strong>Objective: </strong>The objective of this study was to demonstrate structural, physicochemical, and biological similarity between eculizumab RP and SB12 using various state-of-the-art analytical methods.</p><p><strong>Methods: </strong>Comprehensive analytical characterization was conducted with side-by-side comparison of SB12 with European Union (EU) and United States (US) eculizumab RPs using various analytical methods (more than 40 state-of-the-art assays). Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher-order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.</p><p><strong>Results: </strong>Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to the EU and US eculizumab RP. In the structural aspects, it was confirmed that there is no difference between post-translational modification profiles and higher-order structures of SB12 compared with the eculizumab RP. Product-related impurities in the form of aggregates and charge variants were also confirmed to be similar. Mechanism of action (MoA)-related biological activities showed that SB12 is highly similar to the EU and US eculizumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity of comparative binding tendency of SB12 and eculizumab RP to Fc gamma receptors and C1q was confirmed through additional characterization methods. Based on these results, SB12 is expected to have highly similar safety and efficacy compared with eculizumab RP.</p><p><strong>Conclusion: </strong>In summary, the overall analytical characterization and similarity assessment results show that SB12 is highly similar to the EU and US eculizumab RP in terms of structural, physicochemical, biophysical, and biological attributes.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 4","pages":"569-581"},"PeriodicalIF":6.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/04/40259_2023_Article_591.PMC10287819.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.","authors":"Saïf Eddine Zaidi, Eliese Moelker, Kirit Singh, Aditya Mohan, Miguel A Salgado, Muhammed Amir Essibayi, Kelly Hotchkiss, Steven Shen, William Lee, John Sampson, Mustafa Khasraw","doi":"10.1007/s40259-023-00598-2","DOIUrl":"10.1007/s40259-023-00598-2","url":null,"abstract":"<p><p>Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and radiotherapy and further adjuvant chemotherapy if necessary. Despite this regimen, prognosis remains grim. Immunotherapy has shown promising success in a variety of solid tumor types, but efficacy in glioblastoma is yet to be demonstrated. Barriers to the success of immunotherapy in glioblastoma include: a heterogeneous tumor cell population, a highly immunosuppressive microenvironment, and the blood-brain barrier, to name a few. Several immunotherapeutic approaches are actively being investigated and developed to overcome these limitations. In this review, we present different classes of immunotherapy targeting glioblastoma, their most recent results, and potential future directions.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 4","pages":"489-503"},"PeriodicalIF":5.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupus Nephritis: New and Emerging Biologic and Targeted Therapies.","authors":"Ajinath Kale,&nbsp;Maciej Lech,&nbsp;Hans-Joachim Anders,&nbsp;Anil Bhanudas Gaikwad","doi":"10.1007/s40259-023-00597-3","DOIUrl":"https://doi.org/10.1007/s40259-023-00597-3","url":null,"abstract":"<p><p>Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), a polyclonal systemic autoimmunity directed against nuclear and other self-antigens. SLE/LN affects mostly females during childbearing age, which puts them at risk for the progression of chronic kidney disease (CKD), cardiovascular disease, and pregnancy complications. The current management of LN involves the use of drugs with significant toxicities, and despite many attempts at novel drug interventions, the overall treatment efficacy has remained low. In this article, we discuss recent drug approvals and the upcoming pipeline of novel medications tested in clinical trials to improve effectiveness in terms of LN disease activity, LN relapse, and progression of LN-related CKD. In this context, we discuss (1) drugs with the potential to achieve these treatment goals by modulating SLE activity as the driving force for LN (e.g., belimumab, obinutuzumab, anifrolumab, and others); (2) drugs with SLE-non specific renoprotective effects by targeting non-immune mechanisms of LN progression (dapagliflozin, empagliflozin); and (3) drugs with dual immunosuppressive and antiproteinuric effects (voclosporin). Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"37 4","pages":"463-475"},"PeriodicalIF":6.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}