A Phase 1/2 Clinical Trial of Quaratusugene Ozeplasmid and Atezolizumab Maintenance Therapy in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)

This clinical trial will evaluate the combination of quaratusugene ozeplasmid with atezolizumab as maintenance therapy for patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC).
The study is comprised of 2 phases, a dose selection phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2).

开始日期2024-05-09

申办/合作机构

Genprex, Inc.

NCT05062980

/ Terminated临床1期

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Pembrolizumab Versus Docetaxel With or Without Ramucirumab in Patients With Previously Treated Non-Small Cell Lung Cancer

The purpose of this study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa), in combination with pembrolizumab in patients with previously treated NSCLC. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene, and is a systemic gene therapy.
The study will be conducted in 2 phases, a dose escalation phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2). In Phase 1, patients will be enrolled in sequential cohorts treated with successively higher doses of quaratusugene ozeplasmid in combination with pembrolizumab to determine the recommended Phase 2 dose (RP2D). Phase 2 will be comprised of a dose expansion portion and a randomized portion. In the dose expansion portion, patients will be enrolled and treated with quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab. In the randomized portion, patients will be randomized to receive either the investigational treatment of quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab or a control treatment of either docetaxel +/- ramucirumab or the investigator's treatment of choice.
Due to slow enrollment, the Accliam-2 trial was closed in Phase 1 and Phase 2 was not conducted.

开始日期2022-03-30

申办/合作机构

Genprex, Inc.

NCT04486833

/ Recruiting临床1/2期

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer

The purpose of this randomized study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene and is the first systemic gene therapy for cancer.
The study is comprised of a Phase 1 dose escalation portion and two Phase 2 portions evaluating safety and efficacy. Enrollment in the Phase 1 dose escalation portion is complete and the recommended Phase 2 dose (RP2D) was determined. Phase 2a has initiated and enrolled patients are treated with quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy.

开始日期2021-09-03

申办/合作机构

Genprex, Inc.

100 项与 Quaratusugene ozeplasmid 相关的临床结果

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100 项与 Quaratusugene ozeplasmid 相关的转化医学

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100 项与 Quaratusugene ozeplasmid 相关的专利（医药）

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268

项与 Quaratusugene ozeplasmid 相关的文献（医药）

2026-12-01·Molecular Therapy-Nucleic Acids

Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles

Article

作者: Saha, Krishanu ; Murphy, William L ; Scimonelli, Giulia ; Ramamurthy, Apoorva

Human T cells modified with nucleic acids constitute a powerful and emerging therapeutic modality for cancer, autoimmune disorders, and aging-related diseases. However, delivering nucleic acids, such as mRNA encoding synthetic receptors, transcription factors, cytokines, or genome editors to T cells can be challenging, as nucleic acids can unintentionally reduce viable T cell yield and function, particularly when delivered sequentially ex vivo. To address this challenge, we evaluated the efficiency of serial non-viral delivery of synthetic mRNA encapsulated within lipid nanoparticles (LNPs) incorporating cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and fusogenic helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). DOTAP/DOPE-containing LNPs delivered mRNA more efficiently than a clinically benchmarked 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-containing LNP formulation, resulting in significantly higher protein expression in primary human T cells. Furthermore, DOTAP/DOPE-LNP delivery resulted in 100% higher yield of live cells compared to electroporation, an advantage that compounded over serial rounds, with LNP-treated cultures maintaining substantially more viable cells through all four transfections. Additionally, serial transfection of mRNAs encoding a therapeutically relevant chimeric antigen receptor (CAR) payload produced functional CAR T cells. These results demonstrate that LNPs can be a viable platform for serial and iterative T cell engineering using multiple mRNA payloads, providing an alternative to electroporation for the engineering of therapeutic T cells.

2026-10-01·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Microfluidic-assisted formulation of hydrophobic ion pairing-based solid lipid nanoparticles for semaglutide delivery

Article

作者: Racaniello, Giuseppe Francesco ; Cutrignelli, Annalisa ; Siliqi, Dritan ; Tiboni, Mattia ; Pontrelli, Alessia ; Lopedota, Angela Assunta ; Iacobazzi, Rosa Maria ; Arduino, Ilaria ; Denora, Nunzio

Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes and obesity. Despite its clinical efficacy, oral administration remains challenging because of its limited gastrointestinal stability, poor epithelial permeability, and low affinity for lipid-based delivery systems. In the present study, a combined hydrophobic ion pairing (HIP) and solid lipid nanoparticle (SLN) approach was explored to improve semaglutide incorporation and delivery-related properties. Semaglutide was complexed with the cationic lipid DOTAP at different molar ratios (1:0-1:18) and subsequently incorporated into cetyl palmitate-based SLNs produced by microfluidic mixing using a herringbone device. The resulting formulations were characterized in terms of particle size, ζ-potential, encapsulation efficiency, morphology, solid-state organization, colloidal stability, release behavior, mucus interaction, cytocompatibility, and epithelial permeability. Among the various formulations prepared, the one prepared with a molar ratio semaglutide: DOTAP of 1:18 and a peptide concentration of 10% (w/w) (F10) showed the best results, combining particle sizes of less than 300 nm with almost complete encapsulation efficiency and a highly positive ζ-potential. FTIR, DSC, TGA and SAXS analyses confirmed the correct formation of the complex and its incorporation into the lipid matrix. The F10 formulation demonstrated good stability under simulated gastrointestinal conditions and a sustained-release profile. The formulation also exhibited strong interactions with mucus, while retaining the ability to diffuse through the mucin network. Cytocompatibility studies demonstrated acceptable cell viability at relevant concentrations, while permeability experiments through Caco-2 monolayers revealed an approximately 6-fold increase in apparent permeability compared to free semaglutide. Therefore, these findings indicate that the combination of DOTAP-mediated hydrophobic ion pairing and microfluidic-assisted SLN production represents a potentially promising strategy for improving semaglutide encapsulation, gastrointestinal stability, and epithelial transport, while maintaining a favorable balance between mucus interaction and mucodiffusion.

2026-07-01·COLLOIDS AND SURFACES B-BIOINTERFACES

ERG/DOTAP modulation of physiological response to AIE-visualized nanoliposomes is dominated by protein corona

Article

作者: Yu, Bo ; Ding, Meihong ; Cheng, Guilin ; Chen, Keyi ; Ye, Yumeng ; Xie, Ni ; Lu, Shasha ; Zhou, Yu

Lipid nanoparticles (Lips) are studied as drug delivery systems for superior biocompatibility, low toxicity, and high encapsulation efficiency. Their size, charge, and hydrophilicity are tunable via material composition and functional groups for tailored tissue distribution. In biological environments, Lip adsorbs proteins to form a "protein corona (PC)," which alters its physicochemical property and biological interaction. Nevertheless, the mechanisms of PC regulating Lip-tissue targeting remain unclear, with limitations of inaccurate in vivo fluorescence quantification and poor stability. To track Lip fate in vivo, self-synthesized aggregation-induced emission fluorescent nanoparticle (AIEgen R1) was used as a template and encapsulated by Lips with varied material compositions and proportions to prepare visualized nanoliposome R1@Lip. In contrast, using ergosterol (ERG) as membrane material, R1@Lip-4 exhibited fluorescence signals of 55.4 % in liver and 13.3 % in lung tissue, with stronger liver-targeting than cholesterol (CHOL)-based ones. In vitro uptake validated tissue tropism. Proteomic analysis demonstrated that 8 % DOTAP led to an increase in liver-targeting proteins (e.g., TRFE, FIBA), while 30 % DOTAP content resulted in the enrichment of lung-targeting proteins such as ANXA1 and PDLI1. Substituting CHOL with ERG led to a reduction in lung-targeting proteins while increasing liver-targeting proteins (e.g., FIBA). This indicated that R1@Lip-4 with 30 % cationic exhibited a wider liver distribution than R1@Lip-3. These findings establish an "R1@Lip-PC-tissue targeting" relationship, facilitating precise modulation of PC properties through Lip formulation to enhance tissue targeting.

139

项与 Quaratusugene ozeplasmid 相关的新闻（医药）

2026-09-08

·PRNewswire

Genprex to Present at the H.C. Wainwright 28th Annual Global Investment Conference

Company Presentation to Highlight Lead Clinical Oncology Program and Preclinical Diabetes Program AUSTIN, Texas, Sept. 8, 2026 /PRNewswire/ -- Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), today announced that members of its executive leadership team will present at and participate in the H.C. Wainwright 28th Annual Global Investment Conference, being held September 14–16 in New York City. Genprex is a clinical-stage biotechnology company developing gene therapies designed to restore tumor-suppressor function in cancer and insulin-producing function in diabetes. The Company's lead oncology program is in clinical development, and its diabetes program is advancing through preclinical development. Ryan Confer, Genprex's President and Chief Executive Officer, will provide an overview of Reqorsa® Gene Therapy, the Company's lead clinical oncology candidate, and its preclinical diabetes program. He will also discuss the development priorities for each program. Mark Berger, MD, Genprex's Chief Medical Officer, and Thomas Gallagher, Genprex's Senior Vice President of Intellectual Property and Licensing, will also attend the conference and participate in one-on-one investor meetings. Company Presentation Details: Date: Monday, September 14, 2026 Time: 3:30-4 p.m. ET Location: Lotte New York Palace Hotel, Holmes I (4th Floor), New York, NY Registered attendees may request one-on-one meetings with Genprex management via H.C. Wainwright. About Genprex, Inc. Genprex, Inc. is a clinical-stage biotechnology company developing gene therapies designed to restore tumor-suppressor function in cancer and insulin-producing function in diabetes. The Company's lead oncology program is in clinical development, and its diabetes program is advancing through preclinical development. The Company's lead candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid), uses the systemic, non-viral ONCOPREX® Delivery System to deliver the TUSC2 tumor suppressor gene via a non-viral lipid-based nanoparticle. REQORSA is designed to restore tumor-suppressor function and is being evaluated in the Acclaim-1 and Acclaim-3 clinical trials for non-small cell lung cancer and small cell lung cancer, respectively. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to both lung cancer programs and Orphan Drug designation to the small cell lung cancer program. Genprex's preclinical diabetes program is designed to reprogram pancreatic cells and restore insulin-producing function in Type 1 and Type 2 diabetes. The Company is working with academic and research collaborators to optimize candidates, advance manufacturing and prepare for IND-enabling studies. Interested investors and shareholders are encouraged to sign up for press releases and industry updates by visiting the Company Website, registering for Email Alerts and by following Genprex on Twitter, Facebook and LinkedIn. Cautionary Language Concerning Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of management, are not guarantees of performance and are subject to significant risks and uncertainty. These forward-looking statements should, therefore, be considered in light of various important factors, including those set forth in Genprex's reports that it files from time to time with the Securities and Exchange Commission and which you should review, including those statements under "Item 1A – Risk Factors" in Genprex's Annual Report on Form 10-K for the year ended December 31, 2025. Because forward-looking statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Genprex's ability to advance the clinical development, manufacturing and commercialization of its product candidates in accordance with projected timelines and specifications; the timing and success of Genprex's clinical trials, its intended regulatory submissions and any resulting regulatory approvals; the effect of Genprex's product candidates, alone and in combination with other therapies, on cancer and diabetes; Genprex's future growth and financial status, including Genprex's ability to maintain compliance with the continued listing requirements of The Nasdaq Capital Market and to continue as a going concern and to obtain capital to meet its long-term liquidity needs on acceptable terms, or at all; Genprex's commercial and strategic partnerships, including those with its third party vendors, suppliers and manufacturers and their ability to successfully perform and scale up the manufacture of its product candidates; Genprex's intellectual property and licenses; and Genprex's current expectations, estimates, forecasts and projections about the industry and markets in which it operates. These forward-looking statements should not be relied upon as predictions of future events and Genprex cannot assure you that the events or circumstances discussed or reflected in these statements will be achieved or will occur. If such forward-looking statements prove to be inaccurate, the inaccuracy may be material. You should not regard these statements as a representation or warranty by Genprex or any other person that Genprex will achieve its objectives and plans in any specified timeframe, or at all. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Genprex disclaims any obligation to publicly update or release any revisions to these forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release or to reflect the occurrence of unanticipated events, except as required by law. Genprex, Inc. (877) 774-GNPX (4679) GNPX Investor Relations [email protected] GNPX Media Contact Kalyn Dabbs [email protected] SOURCE Genprex, Inc. 21% more press release views with Request a Demo

快速通道临床研究孤儿药

2026-09-05

·生物通

基于白蛋白的阳离子纳米乳用于常氧和低氧条件下原卟啉IX的递送

胶质母细胞瘤是人类最致命的癌症之一，但其治疗受到药物难以穿越血脑屏障的限制。基于白蛋白的纳米材料已成为神经肿瘤学应用中颇具前景的药物递送系统，尤其是用于高级别胶质瘤的治疗。本研究展示了一种负载原卟啉IX（Protoporphyrin IX，PpIX）的人血清白蛋白纳米乳（human serum albumin nanoemulsion，HSANE）作为高级别胶质瘤纳米载体的开发与评估。HSANE采用水包油自发乳化法制备。粒径在200–300 nm之间的纳米颗粒表现出优异的理化性质以及负载PpIX的能力，所得纳米乳的高荧光信号证实了这一点。研究人员在常氧和低氧条件下，对三种高级别胶质瘤细胞系（A-172、U-87 MG和KNS-42）评估了负载PpIX的HSANE的摄取效率和细胞毒性。孵育6小时后，在所有测试的细胞系中均发现PpIX分布于细胞核及核周区域，表明其具有强发射信号，支持其作为诊断标记物载体的潜力。在低氧条件下，HSANE表现出更高的细胞核内化水平。对于所有胶质瘤细胞系，均未观察到细胞毒性。这些结果表明，纳米制剂HSANE作为一种有前景的药物载体和肿瘤标志物递送系统，未来可应用于高级别胶质瘤的治疗与诊断，其高荧光信号可用于高级别胶质瘤的检测、定位和诊断。胶质母细胞瘤治疗与诊断的纳米策略：人血清白蛋白纳米乳递送原卟啉IX的研究解读**一、研究背景与现存问题**胶质母细胞瘤（glioblastoma，GBM）是人类最致命的癌症之一，属于IDH-1/IDH-2野生型的高级别弥漫性胶质瘤，占所有胶质肿瘤的60%–70%，占所有颅内肿瘤的15%。在美国，65岁以上老年患者中GBM的发病率约为13.16/10万。GBM患者的中位生存期仅为术后与治疗后的15–18个月，仅有0.71%的患者在确诊后存活十年以上。GBM治疗耐药和预后不良主要源于以下因素：第一，单个肿瘤细胞可浸润至距肿瘤核心数厘米以外的区域，沿白质纤维束和血管周围间隙播散，累及远处脑实质和深部灰质结构，且这些区域往往存在完整的血脑屏障（blood-brain barrier，BBB）。第二，GBM细胞对标准化疗药物具有高度耐药性，加上BBB对药物通透性的限制，使得药物在肿瘤周边的浓度极为有限。以常用的烷化剂替莫唑胺为例，其在血浆中枢神经系统中的浓度仅为血浆浓度的30%–40%。第三，高度肿瘤细胞异质性和基因组不稳定性导致不同遗传和表观遗传学改变的细胞克隆产生，赋予肿瘤对常规疗法不同程度的抵抗。第四，缺氧肿瘤微环境触发缺氧诱导因子（hypoxia-inducible factors，HIFs）的过表达，该转录因子家族在肿瘤细胞适应低氧张力中发挥关键作用，并激活与细胞增殖、迁移、代谢、肿瘤血管生成、干细胞特性和治疗耐药相关的多个关键基因。当前，仅有少数临床试验探索纳米颗粒用于GBM治疗。GBM模型从临床前研究转化至临床试验的成功率不足8%。迄今为止，尚未有纳米颗粒被报道可同时实现GBM治疗和通过成像辅助诊断或手术切除，从而改善肿瘤定位。根据clinicaltrials.gov的最新检索，仅有两项研究在积极招募纳米颗粒干预的参与者，均与铁纳米颗粒相关，且很少有试验进展超过I期。因此，规避BBB的选择性渗透以更好地递送化疗药物和/或靶向HIF-1通路的生物药物，可能实现更大的治疗效果，具有极其重要的意义。近年来，脂质、聚合物和蛋白质颗粒，特别是白蛋白颗粒，已被证明能够穿越生物膜并将活性药物携带进入活细胞而不破坏膜完整性。既往研究表明，蛋白质药物递送系统与光活性化合物（如酞菁氯化铝）联用，结合可见光照射，可在肿瘤细胞中引起致死性光损伤，可能是治疗恶性胶质瘤的有效工具。商业化药物Abraxane?（白蛋白纳米颗粒负载紫杉醇）已被批准用于癌症治疗，特别是胰腺癌和乳腺癌，凸显了其靶向药物递送的潜力。鉴于肿瘤细胞会从肿瘤表观边界迁移，且缺乏能通过荧光原位检测肿瘤细胞并评估肿瘤范围的技术，研究人员开展本研究，旨在开发一种可高效递送药物以治疗弥漫性胶质瘤的原卟啉IX（Protoporphyrin IX，PpIX）白蛋白纳米乳。该研究描述了一种治疗诊断学策略，使用负载PpIX的人白蛋白纳米乳，产生明确的荧光信号，可在联合抗体、小干扰RNA（small interfering RNA，siRNA）或光（光动力疗法，photodynamic therapy，PDT）时帮助检测、定位、诊断并潜在治疗高级别胶质瘤。**二、主要技术方法**研究人员采用水包油自发乳化法制备人血清白蛋白纳米乳（human serum albumin nanoemulsion，HSANE）。通过光子相关光谱（photon correlation spectroscopy，PCS）测定纳米乳的平均流体动力学直径和多分散指数（polydispersity index，PDI），利用可调谐电阻脉冲传感（Tunable Resistive Pulse Sensing）和透射电子显微镜（transmission electron microscopy，TEM）表征纳米颗粒的粒径分布与形貌。采用紫外-可见吸收光谱和稳态/时间分辨荧光光谱评估PpIX的光物理性质，包括摩尔吸收系数、荧光量子产率和荧光寿命。共聚焦激光扫描显微镜用于观察细胞内摄取和亚细胞定位，并通过Fiji/ImageJ软件的Coloc2插件进行共定位定量分析。MTT比色法用于评估细胞活力，流式细胞术用于细胞周期分析。细胞实验使用三种胶质瘤细胞系：A-172（ATCC? CRL-1620?）、U-87 MG（ATCC? HTB-14?）和KNS-42（里约热内卢细胞库），分别在常氧（pO2 = 20.9%）和低氧（pO2 = 1.0%）条件下进行。**三、研究结果****3.1 白蛋白纳米乳的制备与表征**研究人员选择乳液基质的组成以获得计算亲水亲油平衡值（hydrophilic-lipophilic balance，HLB）为17的配方，该值对应强亲水体系，有利于水包油分散稳定性。HSANE流体动力学尺寸在180天内保持稳定，表明其在水中的稳定性良好，ζ电位呈阳性，归因于DOTAP（dioleoyl-3-trimethylammonium propane）的存在。可调谐电阻脉冲传感和TEM分析确认了负载PpIX的HSANE纳米结构直径在180–400 nm之间，其中75%的颗粒直径在180–250 nm之间。负载PpIX的HSANE在所用合成条件下呈现均匀球形形态，分散性低（±20 nm）。光谱表征方面，游离PpIX在DMSO中呈现404 nm处的Soret带和503、539、572、627 nm处的四个Q带，为PpIX单体的典型特征。荧光光谱显示约632 nm处的发射带，同样为其单体态特征。负载于HSANE中的PpIX在406 nm处吸收系数为66,000 L·mol?1·cm?1，低于游离态值，表明HSANE内部分PpIX发生自聚集。这种自聚集可防止靶细胞外负载PpIX的HSANE产生高荧光信号——细胞摄取后荧光团倾向于在细胞内解聚，增强单体荧光信号，有利于光诊断应用。最佳激发波长位于391–417 nm之间，最佳荧光信号在630–639 nm之间。HSANE中PpIX的荧光量子产率为0.12 ± 0.01，高于有机溶剂中的值，对光诊断应用至关重要。时间分辨荧光显示长寿命约8.7 ns和短寿命约2.0 ns。PpIX在HSANE中的包封效率为71.25% ± 5.3%，这可能与PpIX水溶性低导致药物被包埋于纳米颗粒油核中有关。**3.2 纳米颗粒的体外细胞摄取**研究人员使用三种商业细胞系在常氧和低氧条件（pO2 1.0%）下进行细胞培养实验，每组三次重复。细胞培养图像显示低氧条件下细胞呈现间充质样表型共享。共聚焦显微镜和共定位分析确定了HSANE-PpIX在细胞内的亚定位。在所有测试细胞系中，PpIX均定位于核和核周区域，表明其发射信号强，有利于作为诊断标记物的载体。在低氧条件下，该制剂表现出更高的细胞核内化程度，细胞内颗粒发射的荧光信号增强，可能在体内实体瘤和胶质瘤中实现更好的定位。通过多种相关分析方法对共聚焦图像进行量化验证。共定位分析揭示了不同胶质母细胞瘤细胞系常氧和低氧条件下纳米颗粒与细胞核通道关联的不同特征。6小时为最佳内化时间，所有后续实验均采用此时间点。研究发现，负载于HSANE上的PpIX比DMSO分散的游离PpIX（作为细胞渗透剂）在相同颗粒浓度下具有更高的荧光发射。这一发现强有力地证明HSANE提高了PpIX在以水为主的细胞环境中的生物利用度和细胞摄取，克服了载体辅助递送的局限性，与既往报道一致。常氧条件下各细胞系摄取率不同，其中A-172摄取最高。低氧条件下所有细胞摄取率几乎相同，但A-172仍显示高出两倍的摄取，这归因于其高代谢率，这也证实了实体瘤需要采用低氧条件进行研究。这与Yang等人的观察一致，即含白蛋白纳米颗粒在深部胶质母细胞瘤和缺氧环境中的积累可能得到促进，因为白蛋白结合蛋白介导的转运可能发生，促进摄取、穿越血脑屏障并增加到达肿瘤细胞的能力。此外，白蛋白纳米颗粒可通过特定机制（被动或主动）轻松穿透BBB，如SPARC和gp60介导的仿生转运。**3.3 细胞毒性与细胞周期分析**通过MTT实验评估了HSANE和PpIX负载制剂的细胞毒性，以确定胶质瘤细胞的无毒浓度阈值。与对照组相比，空纳米载体和包封的PpIX均未表现出暗毒性。这些发现与既往研究一致，表明白蛋白纳米颗粒作为癌症治疗中的安全和仿生平台。为进一步确定治疗窗口，研究人员还评估了630 nm光照射的效果。在所研究的浓度和不同光剂量下均未观察到光毒性效应。这些数据表明，细胞内PpIX浓度低于产生细胞毒性活性氧（reactive oxygen species，ROS）所需的阈值，同时超过荧光成像的检测限。这种双重特性支持将该制剂开发为非破坏性诊断纳米工具。流式细胞术用于评估细胞周期改变，基于碘化丙啶（propidium iodide，PI）染色后细胞DNA含量的单变量分析及DNA含量频率直方图的去卷积。A-172即使在PpIX高浓度下也与制剂具有更高的相容性。对于U-87 MG和KNS-42细胞系，浓度高达1.0 μmol·L?1的处理未显示统计学差异，表明应用是安全的。细胞系分类可能解释基于基因表达的细胞活力差异。间充质亚型U-87 MG和KNS-42对TNFRSF1A和MGMT基因的抵抗力较低。相反，A-172被分类为前神经亚型，与三羧酸循环相关基因（如IDH-1）的突变相关，该突变导致功能获得性酶活，产生异常的促癌代谢产物2-HG，可能促进肿瘤发生和广泛的超甲基化表型。该亚型还与血小板衍生生长因子受体α的扩增相关，该受体对脑发育至关重要，但与INK4A/ARF缺失相关时其过表达与胶质瘤发生相关。**四、讨论与结论**尽管GBM的诊断和治疗取得了进展，但作为高度侵袭性肿瘤，仍存在显著差距。当前临床试验中技术转化的可行选择有限，凸显了对改进设计、质量控制和方案标准化的持续需求。因此，纳米颗粒的开发需要高度结构化和严格的方法。所开发的纳米制剂目前处于TRL 4级评估阶段，作为GBM的双重诊断和治疗制剂具有前景，在光疗方面具有特异性疗效。本研究合成并表征了一种高稳定性杂化白蛋白纳米乳HSANE，其阳离子特性与PpIX相容。在体外剂量高达3.0 × 10?6 mol·L?1时未观察到毒性。在所有评估的细胞系中，HSANE定位于细胞核和核周区域并产生强信号，凸显其作为诊断标记物载体的可行性。剂量高达3.0 × 10?6 mol·L?1时未观察到细胞毒性和光毒性。所有观察结果表明，HSANE是一种有前景的药物载体递送系统，可用于光诊断和胶质母细胞瘤治疗。从临床转化的角度来看，小尺寸、高荧光、选择性摄取和低毒性是极为有利的特性。利用这种类型的纳米颗粒，可以穿过BBB，在PDT方法中产生ROS，并降低噪声比，这对术中切缘界定很重要。未来工作应在药物释放、遗传毒性和剂量-反应效应方面对该制剂进行更深入的研究。

临床研究

2026-09-04

·PRNewswire

Andelyn Biosciences to Scale Manufacturing for Genprex's Diabetes Gene Therapy Program

The collaboration will support Genprex's AAV-based diabetes gene therapy candidate for IND-enabling preclinical studies and cGMP clinical manufacturing. Sept. 1, 2026 -- Andelyn Biosciences, a leading contract development and manufacturing organization, announced today that Genprex, Inc. has selected Andelyn to support scale-up manufacturing for its diabetes gene therapy program. Genprex's diabetes gene therapy candidate is designed to deliver the Pdx1 and MafA genes directly to the pancreas via the pancreatic duct using an AAV vector. The program is being developed as a potential treatment for Type 1 and Type 2 diabetes. Under the agreement, Andelyn will transition Genprex's adeno-associated virus (AAV)-based diabetes gene therapy candidate with process optimization, scale-up, and IND-enabling and clinical-stage manufacturing to support clinical trials. The collaboration will draw on Andelyn's Curator® Cell and Gene Therapy Platform and experience in AAV process development, technology transfer, analytical development, and cGMP manufacturing. Manufacturing activities are expected to include process optimization, scale-up, analytical qualification, potency assay development, and drug product manufacturing in a cGMP-compliant facility. In Type 1 diabetes, Genprex's candidate is designed to transform pancreatic alpha cells into functional beta-like cells capable of producing insulin. Genprex has reported preclinical findings in Type 1 diabetes mouse models showing restoration of normal blood glucose levels for an extended period, as well as findings in nonhuman primate models indicating reduced insulin requirements, increased C-peptide levels, and improved glucose tolerance. For Type 2 diabetes, where autoimmunity is not a primary driver of disease, Genprex is evaluating whether its approach may help replenish and rejuvenate exhausted insulin-producing beta cells. The company has reported preclinical activity in both mouse and nonhuman primate models. "Andelyn is pleased to support Genprex as it advances this important diabetes gene therapy program," said Matt Niloff, CCO at Andelyn. "The transition from academic or research-grade manufacturing to a scalable cGMP process is a pivotal step in developing an advanced therapy. Our team will provide the technical, operational, and quality expertise needed to establish a robust manufacturing foundation for Genprex's upcoming preclinical and clinical milestones." "Selecting Andelyn marks an important step in preparing our diabetes gene therapy program for IND-enabling studies and future clinical evaluation," said Ryan Confer, President and Chief Executive Officer of Genprex. "Andelyn's experience in AAV development and cGMP manufacturing will help us advance the manufacturing process as we work to move this program toward the clinic." Andelyn Biosciences is a full-service cell and gene therapy CDMO focused on developing, characterizing, and producing viral vectors for gene therapy. With more than 20 years of experience, Andelyn's deep scientific expertise has resulted in the production of cGMP material for more than 500 clinical batches and 85 global clinical trials. Operating out of its development and manufacturing facilities in Columbus, Ohio, Andelyn supports its clients in developing cell and gene therapies from concept through plasmid engineering and manufacturing, process and analytical development, and cGMP clinical and commercial manufacturing. Andelyn can accelerate programs and deliver high-quality products by developing and manufacturing processes on its configurable, data-driven Curator® Cell and Gene Therapy Platforms, or by tech transfer within an established client program. Capabilities include cGMP manufacturing for suspension and adherent processes. A rigorous, commercial-grade quality system, phase-appropriate manufacturing, and supply chain vertical integration further help clients bring critical therapies to market. Genprex, Inc. is a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes. Genprex's technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. Genprex's oncology program utilizes its systemic, non-viral Oncoprex® Delivery System which encapsulates the gene-expressing plasmids using lipid-based nanoparticles in a lipoplex form. The resultant product is administered intravenously, where it is taken up by tumor cells that then express tumor suppressor proteins that were deficient in the tumor. The Company's lead product candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid), is being evaluated in two clinical trials as a treatment for NSCLC and SCLC. Each of Genprex's lung cancer clinical programs has received a Fast Track Designation from the FDA for the treatment of that patient population, and Genprex's SCLC program has received an FDA Orphan Drug Designation. Genprex's diabetes gene therapy approach is comprised of a novel infusion process that uses an AAV vector to deliver Pdx1 and MafA genes directly to the pancreas. In models of Type 1 diabetes, GPX-002 transforms alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body's immune system. In a similar approach for Type 2 diabetes, where autoimmunity is not at play, GPX-002 is believed to rejuvenate and replenish exhausted beta cells. The content above comes from the network. if any infringement, please contact us to modify.

孤儿药基因疗法引进/卖出快速通道临床研究

100 项与 Quaratusugene ozeplasmid 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
广泛期小细胞肺癌	临床2期	美国	Genprex, Inc.	2024-05-09
EGFR突变的非小细胞肺癌	临床2期	美国	Genprex, Inc.	2021-09-03
复发性非小细胞肺癌	临床2期	美国	Genprex, Inc.	2014-02-01
转移性非小细胞肺癌	临床1期	美国	Genprex, Inc.	2022-03-30
ALK阳性非小细胞肺癌	临床前	美国	Genprex, Inc.	2025-10-14
间皮瘤	临床前	美国	Genprex, Inc.	2025-04-01
乳腺癌	临床前	美国	Genprex, Inc.	2019-08-30

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Clin Lung Cancer 人工标引	临床1期	EGFR突变的非小细胞肺癌 EGFR Mutation	12	Osimertinib + Quaratusugene ozeplasmid	醖鏇夢憲鹽觸鬱餘遞願(繭壓壓獵鬱衊窪鑰獵觸) = 衊壓餘壓淵衊糧鑰觸選餘遞窪窪簾鏇積窪願繭 (艱夢鹽鑰鹽廠鏇鏇獵選 )	积极	2025-11-17
NCT05703971 (Acclaim-3, PipelineReview) 人工标引	临床1/2期	广泛期小细胞肺癌维持	1	REQORSA and Tecentriq	簾選壓築遞繭憲獵淵膚(襯繭餘願遞鏇製簾獵衊) = 夢壓簾選鏇窪窪淵糧蓋淵憲構艱積獵憲廠選夢 (簾膚糧淵鹹壓範網顧壓 )	积极	2024-08-14
NCT04486833 (Acclaim-1, PipelineReview) 人工标引	临床1/2期	非小细胞肺癌	2	REQORSA + Tagrisso	壓簾願獵糧膚簾製憲鏇(鏇壓遞膚淵製觸顧襯蓋) = 淵顧蓋淵鑰簾網築鏇獵襯艱憲鏇範簾繭糧餘餘 (蓋製醖窪艱製築簾壓蓋 )	积极	2024-08-14
NCT04486833 (Acclaim-1, ASCO 12023 \| ASCO 22023) 人工标引	临床1/2期	非小细胞肺癌	8	Osimertinib+Quaratusugene ozeplasmid	淵蓋窪淵築艱遞鹹簾製(繭構鑰淵醖鹹憲繭膚鑰) = 鹹獵簾鏇範構夢廠餘醖壓醖鑰齋簾範構顧簾鹹 (鬱廠繭鹽鏇鬱醖遞鑰築 ) 更多	积极	2023-05-26
NCT00059605 (Pubmed \| PLoS One)	临床1期	晚期非小细胞肺癌	-	DOTAP:chol-TUSC2	壓鑰觸繭簾遞淵膚鹽壓(範遞鹽窪廠範繭衊膚鏇) = 夢繭繭選鹹繭構觸壓憲築衊窪鹹壓鑰膚膚構簾 (獵顧壓醖醖鏇淵膚鏇觸 )	-	2012-04-25