A First in Human, Phase 1/2a, Multicentre, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of PBP1510 in Patients With Advanced/Metastatic Pancreatic Cancer

The first in human clinical study is planned as an open-label, dose-escalation, and dose-expansion, multicentre, two-part, Phase 1/2a study of PBP1510 administered to patients with advanced/metastatic pancreatic cancer. The study will be conducted in two parts, Part 1 as a PBP1510 single agent dose-escalation, and PBP1510 dose-escalation in combination with gemcitabine, and Part 2 as PBP1510 dose-expansion at the RP2D in combination with gemcitabine.

开始日期2023-06-05

申办/合作机构

Prestige BioPharma Ltd.

EUCTR2021-000682-32-ES / Unknown status临床1/2期

A First in human, Phase 1/2a, Multicentre, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of PBP1510 in Patients with Advanced/Metastatic Pancreatic Cancer

开始日期2022-02-16

申办/合作机构

Prestige BioPharma Ltd.

100 项与 ZG16B 相关的临床结果

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100 项与 ZG16B 相关的转化医学

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0 项与 ZG16B 相关的专利（医药）

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项与 ZG16B 相关的文献（医药）

2024-10-21·Oncogene

ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer

Article

作者: Li, Ling ; Zhang, Mingzhi ; Li, Yizhen ; Nan, Manman ; Meng, Hui ; Ding, Yi

Dendritic cells (DCs) are critical mediators of antigen priming and T-cell activation. Zymogen granule protein 16 (ZG16) is demonstrated as an anti-oncogene in T-cell mediated antitumor immunity, but its effect on DCs is largely unknown. Herein, we wonder whether ZG16 affects the activation of DCs in pancreatic cancer. Firstly, the increased ZG16 expression was observed during the maturation of DCs derived from mouse bone marrow or human peripheral blood. Then, overexpression of ZG16 or exogenous introduction of recombinant ZG16 protein induced the expression of MHC II, CD86, CD84, and CCR7 on the surface of DCs, thereby facilitating the secretion of proinflammatory mediators IL-1β, IL-6, TNF-α, and IL-12/p70, supporting the promoting effect of ZG16 on DC maturation. By establishing the subcutaneous and orthotopic mouse models of pancreatic cancer, we confirmed that intraperitoneal injection of recombinant ZG16 protein (Re-mZG16) could induce tumor regression by stimulating DC maturation and enhancing antitumor responses of CD4 + , CD8 + , PD-1 + , and Ctla4+ cells. Besides, Re-mZG16 in combination with gemcitabine showed a synergistic effect in the treatment of pancreatic cancer. Mechanistically, we demonstrated that ZG16 inhibited the ubiquitination and degradation of CD40, which depended on the lectin domain of ZG16. In conclusion, this study provided a novel insight into the role of ZG16-CD40 axis in DC-based immunotherapy for pancreatic cancer.

2024-10-01·Journal of Clinical Periodontology

Using SWATH‐MS to identify new molecular biomarkers in gingival crevicular fluid for detecting periodontitis and its response to treatment

Article

作者: Alonso‐Sampedro, M. ; Relvas, M. ; Balsa‐Castro, C. ; Tomás, I. ; Regueira‐Iglesias, A. ; Blanco‐Pintos, T. ; Chantada‐Vázquez, M. P.

AbstractAimTo identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra (SWATH‐MS).Materials and MethodsGCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III–IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH‐MS, and proteins were identified by the UniProt human‐specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions.ResultsIn the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias‐corrected (bc)‐sensitivity/bc‐specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP‐9, MMP‐8, zinc‐α‐2‐glycoprotein and neutrophil gelatinase‐associated lipocalin and ZG16B with cornulin provided increased bc‐sensitivity/bc‐specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions.ConclusionsNew single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings.

2023-05-30·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals

1区 · 综合性期刊

Article

作者: McPherson, Robert L. ; Isabella, Christine R. ; Ruhl, Stefan ; Tettelin, Hervé ; Putnik, Rachel ; Dodge, Gregory J. ; Ghosh, Soumi ; Ahearn, Christian P. ; Bartlett, Helen ; Grimes, Catherine L. ; Kiessling, Laura L. ; Jain, Shikha ; Dugan, Amanda E. ; Neznanova, Lubov ; Imperiali, Barbara ; Marando, Victoria M.

The oral microbiome is critical to human health and disease, yet the role that host salivary proteins play in maintaining oral health is unclear. A highly expressed gene in human salivary glands encodes the lectin zymogen granule protein 16 homolog B (ZG16B). Despite the abundance of this protein, its interaction partners in the oral microbiome are unknown. ZG16B possesses a lectin fold, but whether it binds carbohydrates is unclear. We postulated that ZG16B would bind microbial glycans to mediate recognition of oral microbes. To this end, we developed a microbial glycan analysis probe (mGAP) strategy based on conjugating the recombinant protein to fluorescent or biotin reporter functionality. Applying the ZG16B-mGAP to dental plaque isolates revealed that ZG16B predominantly binds to a limited set of oral microbes, including Streptococcus mitis, Gemella haemolysans , and, most prominently, Streptococcus vestibularis. S. vestibularis is a commensal bacterium widely distributed in healthy individuals. ZG16B binds to S. vestibularis through the cell wall polysaccharides attached to the peptidoglycan, indicating that the protein is a lectin. ZG16B slows the growth of S. vestibularis with no cytotoxicity, suggesting that it regulates S. vestibularis abundance. The mGAP probes also revealed that ZG16B interacts with the salivary mucin MUC7. Analysis of S. vestibularis and MUC7 with ZG16B using super-resolution microscopy supports ternary complex formation that can promote microbe clustering. Together, our data suggest that ZG16B influences the compositional balance of the oral microbiome by capturing commensal microbes and regulating their growth using a mucin-assisted clearance mechanism.

项与 ZG16B 相关的新闻（医药）

2024-10-29

·生物制品圈

中南大学：揭示头颈部鳞状细胞癌预后新指标，开启免疫治疗新篇章

【导读】最近的研究强调了免疫反应的表观遗传调节，然而，RNA N6-甲基腺苷（m6A）对于头颈部鳞状细胞癌（HNSC）的修饰和免疫调节，仍未被探索。 2024年10月26日，中南大学附属湘雅三医院Gao Ru团队在期刊《Heliyon》上发表了题为“The m6A and immune regulatory gene signature predicts the prognosis and correlates with immune infiltration of head and neck squamous cell carcinoma”的研究论文。研究结果证实，与 m6A相关的聚类亚群、风险模型和免疫调节基因，预示着HNSC的不良预后。风险评分成为HNSC患者的有效预后生物标志物和预测指标。 https://www.cell.com/heliyon/fulltext/S2405-8440(24)15789-1#au4 关于头颈部鳞状细胞癌 01 头颈部鳞状细胞癌（HNSC）在全球最普遍的恶性肿瘤中排名第六。尽管在过去30年中，HNSC的存活率略有提高，但这种情况造成了深远的损失，严重影响了患者的身心健康。传统的诊断和治疗方法，对早期疾病检测和预后增强构成挑战。近年来，多项研究揭示了m6A和免疫调节之间的独特关系改良。这种相互作用包括T细胞增殖和分化的修饰、必需宿主转录物周转的调节以及甲基化病毒转录物，以促进宿主免疫系统的逃避。本研究利用癌症基因组图谱（TCGA）数据库，研究与m6A调节因子和免疫调节相关差异表达基因（M6A&IMRDEGs）介导的甲基化修饰相关的生物学功能和网络，旨在阐明M6A&IMRDEGs在HNSC患者预后中的作用。头颈部鳞状细胞癌预后风险模型的分析 02 与低风险组相比，高危组的预后较差。团队观察到风险水平与3个临床因素（性别、年龄和M阶段）之间存在统计学上的显著关联。M阶段在预后风险模型中，表现出比其他变量更高的效用，而Gender表现出较低的效用。预后风险模型在1年>3年>5年时，表现出优异的临床预测效果。预后分析免疫浸润分析 03 高危组和低危组之间各种免疫细胞的表达水平差异有统计学意义，包括活化的B细胞、活化的CD4 T细胞、活化的CD8 T细胞、效应记忆CD8 T细胞、未成熟B细胞、记忆B细胞、滤泡状T辅助细胞、1型T辅助细胞、17型T辅助细胞、2型T辅助细胞、活化的树突状细胞、嗜酸性粒细胞、未成熟树突状细胞、巨噬细胞、MDSC、单核细胞、自然杀伤T细胞和中性粒细胞。在高危组中，团队观察到MUC5B与活化的树突状细胞之间存在显著的正相关；而在低风险组中，SCGB3A1与活化的CD4 T细胞呈显著负相关。通过ssGSEA算法，进行风险组免疫浸润分析。总结 04 1. 研究发现29个m6A和IMRDEG（免疫调节相关基因）的差异表达，并通过GO、CNV、SNP评估和WGCNA分析，鉴定出与HNSC预后相关的基因，如IL11和MMP13。 2. 通过PPI分析，确定7个与m6A修饰和免疫调节有关的中心基因，包括BPIFB1、BPIFB2、GP2、MUC5B、MUC7、PIP和SCGB3A1。 3. 高危组和低危组之间存在18种免疫细胞类型的表达水平差异，表明风险模型可以评估肿瘤的免疫状态并预测治疗结果。 4. 确定了9个关键基因（HTN1、ZG16B、HMGA2、GAST、LYZ、CSF2、MB、MAGEB2和TAC1）构建的风险评分，与HNSC患者的性别、年龄和M分期相关，是预后不良的独立危险因素。 5. 研究还发现与HNSC发生和发展相关的DEGs（差异表达基因），主要与细胞外基质（ECM）结构和免疫反应有关。 6. 研究提供了HNSC中M6A&IMRDEGs的全面调查，并开发了相关的预后风险模型，有助于识别肿瘤的免疫表型，为个性化癌症免疫治疗提供新见解，但需要进一步验证。参考资料： 1.Ferlay, J. ... Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.Int. J. Cancer. 2018; 144:1941-1953 2.Saleh, K. ...New developments in the management of head and neck cancer – impact of pembrolizumab.Therapeut. Clin. Risk Manag. 2018; 14:295-303

免疫疗法

2023-03-21

·BioSpace

Prestige Biopharma Receives FDA Fast Track Designation for PBP1510 in the Treatment of Pancreatic Cancer

SINGAPORE--(BUSINESS WIRE)-- Prestige Biopharma has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for PBP1510 (International Non-proprietary name: Ulenistamab), in the treatment of unresectable or metastatic pancreatic adenocarcinoma (PDAC) that has relapsed following and/or is refractory to at least one line of prior therapy. PBP1510 targets Pancreatic Adenocarcinoma Upregulated Factor (PAUF), a tumour-specific protein, found to be overexpressed in majority of pancreatic cancer cases. PAUF overexpression promotes key cellular functions, including proliferation, migration, invasion, and growth of pancreatic cancer cells, and contributes to the development of acquired resistance to chemotherapeutic agents. PBP1510 is designed to target these key biological mechanisms that results in limited effectiveness of current treatment options and rapid progression of pancreatic cancer. By effectively inhibiting the tumorigenic effects of PAUF overexpression in preclinical models, PBP1510 represents a promising therapeutic strategy for addressing the unmet medical needs of pancreatic cancer patients. A global Phase 1/2a clinical trial is currently underway in the United States, Europe, and Asia, with the aim of bringing this innovative therapy to the clinic. The first-in-human Phase 1/2a study is an open-label, multicentre, two-part study in patients with advanced/metastatic pancreatic cancer. Phase 1 is a dose-escalation phase, wherein PBP1510 will be administered, either as monotherapy or in combination with gemcitabine, in two separate dose-escalation cohorts. From Phase 1 part of the study a recommended Phase 2a dose (RP2D) will be determined based on the analysis of pharmacokinetics, safety, and efficacy data. Phase 2 is a dose-expansion phase, wherein PBP1510 at the RP2D in combination with gemcitabine will be administered to evaluate efficacy and safety of PBP1510. Overall, the Phase 1/2a study aims to collect important safety data on the use of PBP1510 as a monotherapy or in combination with gemcitabine and explore the efficacy of a combined PBP1510 and gemcitabine regimen. The study will substantiate the preclinical findings of PBP1510’s synergistic antitumour activity in combination therapy with gemcitabine without increased toxicity, as anticipated from their distinct mechanisms of action. With Fast Track designation from the FDA, PBP1510 represents a promising advancement in the treatment of pancreatic cancer. Prestige Biopharma intends to take full advantage of the benefits offered by the designation to provide faster access for patients in need. View source version on businesswire.com: Contacts info@prestigebio.com Source: Prestige Biopharma Limited View this news release online at:

快速通道临床1期临床2期

2023-03-10

·NS Medical Devices

Prestige Biopharma develops diagnostic kit for early detection of pancreatic cancer

The company’s new diagnostic kit is designed to measure the levels of Pancreatic Adenocarcinoma Upregulated Factor (PAUF), a tumour-specific biomarker that is overexpressed in around 80% of pancreatic cancer cases Prestige Biopharma develops pancreatic cancer early diagnostic kit. (Credit: CDC on Unsplash) Singapore-based biopharmaceutical company Prestige Biopharma has developed an advanced diagnostic test kit for detecting pancreatic cancer. The company’s new diagnostic kit is designed to measure the levels of Pancreatic Adenocarcinoma Upregulated Factor (PAUF). PAUF is a tumour-specific biomarker that is overexpressed in around 80% of pancreatic cancer cases, correlated with early progression and metastasis. The novel diagnostic method exhibits high sensitivity and specificity in detecting PAUF. In the preliminary investigations by the company’s Innovative Discovery Centre (IDC), pancreatic cancer patients had a higher level of PAUF expression than healthy individuals. The Receiver Operating Characteristic (ROC) analysis is used to evaluate a biomarker’s effectiveness, showing 86.3% sensitivity in detecting pancreatic cancer. Prestige Biopharma CEO Lisa S Park said: “The early detection of pancreatic cancer is just as crucial as an effective treatment, given its reputation as a silent killer. “As part of our efforts to combat this devastating disease, we are expanding into diagnostics using our innovative PAUF-based technology. “Through the successful development of the diagnostic kit on top of a novel antibody, we believe our efforts will significantly benefit patients with pancreatic cancer and contribute to improving human health, which is exactly what our mission ‘Innovation for Life’ stands for.” Pancreatic cancer is an aggressive tumour associated with extremely poor prognosis and low survival rates, due to late diagnosis, non-specific symptoms, early metastasis, rapid progression, and the lack of effective treatment modalities. The company has submitted a provisional patent application for the diagnostic method in South Korea and started partnership discussions with major diagnostic companies. In addition, the company’s Contract Development and Manufacturing Organization (CDMO), Prestige Biologics, is preparing to manufacture antibody diagnostic kits. Prestige Biopharma has been developing PBP1510, an advanced anti-PAUF monoclonal antibody to treat pancreatic cancer. PBP1510 secured the US Food and Drug Administration (FDA) Orphan Drug designation, the European Medicines Agency (EMA), and the Ministry of Food and Drug Safety (MFDS) in 2020.

孤儿药临床结果诊断试剂