Lomustine

PARIS--(BUSINESS WIRE)--Carthera, developer of the revolutionary SonoCloud® medical device, today announces it has enrolled the first 100 patients in its SONOBIRD pivotal trial for the treatment of recurrent glioblastoma. A spin-off of Sorbonne University founded by noted neurosurgeon Prof. Alexandre Carpentier, Carthera reaches this milestone as it prepares to conduct the largest clinical trial ever using ultrasound for the temporary opening of the blood-brain-barrier (BBB) in patients with recurrent glioblastoma. Nearly all 40 participating sites across Europe and the U.S. are now active. Carthera anticipates that recruitment will continue swiftly to reach the 560 patients planned for the study. The trial (NCT05902169) is the world’s first randomized, multicentric, two-arm pivotal trial of BBB opening prior to chemotherapy injection in recurrent glioblastoma patients. Notably, the trial makes use of the SonoCloud, an innovative ultrasound-based medical device developed by Carthera to treat a wide range of brain disorders. Specifically, the trial compares the use of SonoCloud combined with carboplatin versus standard therapies in patients with a first recurrence of glioblastoma. “It has been a privilege to offer this trial to patients with recurrent glioblastoma. The underlying concept is highly promising, device implantation has proceeded smoothly and patients have shown strong interest in participating,” said Dr. Brian Gill, assistant professor of neurosurgery at Columbia University Irving Medical Center in New York. “We desperately need new treatments for patients with recurrent glioblastoma. SonoCloud has the potential to transform our ability to deliver a high dose of therapeutics to the brain,” said Dr. Marjolein Geurts, neuro‐oncologist at Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. To date, more than 550 SonoCloud treatments have been performed worldwide, confirming Carthera’s position as a leader in the field of ultrasound-based BBB opening, as well as the growing interest in SonoCloud as a potentially viable new treatment option for patients with recurrent glioblastoma. “Our progress in recruiting patients reflects the engagement and strong support from our clinical sites, and from the neuro-oncology and surgery community, in advancing innovative therapies,” said Carole Desseaux, chief clinical officer at Carthera. “We are very grateful for the commitment and enthusiasm of the patients and clinicians who are taking part in this trial.” “Achieving this milestone is an important step in introducing our SonoCloud device to the large patient population urgently in need of solutions to improve treatment outcomes,” said Frederic Sottilini, CEO of Carthera. “With its breakthrough device and orphan drug designations, Carthera remains committed to transforming glioblastoma treatment and to acquiring market access for its groundbreaking technology.” Initiated in February 2024, the registrational study aims to enroll a total of 560 US and EU patients within two years, with a view to obtaining marketing authorization. The first interim analysis of the clinical data will be available soon. About the SONOBIRD trial The open-label, comparative, randomized, multicenter, two-arm clinical trial with a 1:1 ratio aims to evaluate overall survival in patients undergoing carboplatin chemotherapy and treated with the SonoCloud system to open the Blood-Brain Barrier (BBB). This is compared to the medical consensus recommended regimens (lomustine or temozolomide). The trial also evaluates the effectiveness of the SonoCloud and carboplatin treatment in delaying or slowing tumor growth. The SONOBIRD trial follows on from the SC9-GBM-01 trial, which demonstrated the feasibility and the safety profile of SonoCloud, as well as the potential of carboplatin tested as a monotherapy in combination with BBB opening. About SonoCloud SonoCloud® is an innovative medical device developed by Carthera. It emits ultrasound to temporarily increase the permeability of the blood vessels in the brain to improve the delivery of therapeutic molecules. Invented by Prof. Alexandre Carpentier and developed in collaboration with the Laboratory of Therapeutic Applications of Ultrasound (Laboratoire Thérapie et Applications Ultrasonores, LabTAU, INSERM) in Lyon, France, SonoCloud is an implant inserted into the skull and activated prior to injection of a therapeutic agent. Several minutes of low-intensity ultrasound opens the blood-brain barrier for six hours and increases the concentration of therapeutic molecules in the brain. This ultrasound-induced opening of the blood-brain barrier is a world-first. It offers a new treatment option for a wide range of indications, including brain tumors and Alzheimer’s disease. SonoCloud is an investigational product, the device has not yet received EMA or FDA approval. About Carthera Carthera is a clinical-stage medtech company focused on developing innovative ultrasound-based medical devices to treat a wide range of brain disorders. The company is a spin-off from AP-HP Paris and Sorbonne University. Carthera leverages the inventions of Prof. Alexandre Carpentier, head neurosurgeon at AP-HP Sorbonne university, who has achieved worldwide recognition for his innovative developments in treating brain disorders. Carthera is developing SonoCloud®, an intracranial implant that temporarily opens the blood-brain barrier. The device is currently in clinical trials in Europe and the United States. It received FDA Breakthrough Device Designation in 2022, and FDA/EMA Orphan Drug Designation in 2023 for carboplatin when used with SonoCloud. Founded in 2010 by Prof. Alexandre Carpentier, run by CEO Frederic Sottilini and chaired by Oern Stuge, MD, Carthera has offices in France (Lyon and Paris) and a subsidiary in Boston, Massachusetts. Since its inception, the technical and clinical development of SonoCloud has received support from the National Research Agency (ANR), the French public investment bank (Bpifrance), the National Institutes of Health (NIH) and the European Innovation Council (EIC). Additional information is available at www.carthera.eu.

4月4日，中南大学湘雅医院研究人员在期刊《Journal of Experimental & Clinical Cancer Research》上发表了研究论文，题为“TRAF7 knockdown induces cellular senescence and synergizes with lomustine to inhibit glioma progression and recurrence”，本研究中，研究人员发现TRAF7 可作为预测性生物标志物，并且在（NCCN）治疗指南中，对于胶质瘤的进展和复发而言，它可能是一个潜在的治疗靶点。对于 TRAF7 高表达的胶质瘤患者，洛莫司汀（一种能调节细胞衰老和细胞周期的药物）可能是优先选择。 4月4日，中南大学湘雅医院研究人员在期刊《Journal of Experimental & Clinical Cancer Research》上发表了研究论文，题为“TRAF7 knockdown induces cellular senescence and synergizes with lomustine to inhibit glioma progression and recurrence”，本研究中， 研究人员发现TRAF7 可作为预测性生物标志物，并且在（NCCN）治疗指南中，对于胶质瘤的进展和复发而言，它可能是一个潜在的治疗靶点。 对于 TRAF7 高表达的胶质瘤患者，洛莫司汀（一种能调节细胞衰老和细胞周期的药物）可能是优先选择。 https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03363-1 https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03363-1 研究背景 研究背景 01 01 源自神经胶质细胞或前体细胞的神经胶质瘤是原发性脑恶性肿瘤中最常见且最具侵袭性的类型，占中枢神经系统恶性肿瘤的 80.9%。脑恶性肿瘤包括高级别神经胶质瘤（HGG，III - IV 级）和低级别神经胶质瘤（LGG，I - II 级）。HGGs主要依赖于全切除，术后辅助放化疗可降低复发率，延长总生存期。然而，五年生存率通常低于 10%。约 52% - 62% 的 LGG 患者在 5 年内复发，这些复发的 LGG 患者存在进展为 HGG 的高风险，最终导致不良的生存预后。生物标志物是与神经胶质瘤预后相关的重要因素，包括 IDH 突变、CDKN2a 缺失和 TERT 启动子突变。细胞衰老广泛存在于脑癌的肿瘤发生过程中，基于分析，探索潜在的衰老相关检查点是不良预后亚型神经胶质瘤中的一个重要临床问题。 源自神经胶质细胞或前体细胞的神经胶质瘤是原发性脑恶性肿瘤中最常见且最具侵袭性的类型，占中枢神经系统恶性肿瘤的 80.9%。脑恶性肿瘤包括高级别神经胶质瘤（HGG，III - IV 级）和低级别神经胶质瘤（LGG，I - II 级）。HGGs主要依赖于全切除，术后辅助放化疗可降低复发率，延长总生存期。然而，五年生存率通常低于 10%。约 52% - 62% 的 LGG 患者在 5 年内复发，这些复发的 LGG 患者存在进展为 HGG 的高风险，最终导致不良的生存预后。生物标志物是与神经胶质瘤预后相关的重要因素，包括 IDH 突变、CDKN2a 缺失和 TERT 启动子突变。细胞衰老广泛存在于脑癌的肿瘤发生过程中，基于分析，探索潜在的衰老相关检查点是不良预后亚型神经胶质瘤中的一个重要临床问题。 细胞衰老是指由多种应激源（包括致癌激活和化疗药物）触发的细胞分裂永久停止。衰老细胞通过激活p53/p21CIP1和p16INK4a/Rb肿瘤抑制信号通路退出细胞周期。诱导细胞衰老是一种抗肿瘤屏障，在细胞外源性环境中，衰老相关分泌表型（SASP）进一步增强了细胞的肿瘤抑制功能。研究人员已经证明，CITK缺失可诱导依赖p53的衰老，从而限制髓母细胞瘤的增殖。 细胞衰老是指由多种应激源（包括致癌激活和化疗药物）触发的细胞分裂永久停止。衰老细胞通过激活p53/p21CIP1和p16INK4a/Rb肿瘤抑制信号通路退出细胞周期。诱导细胞衰老是一种抗肿瘤屏障，在细胞外源性环境中，衰老相关分泌表型（SASP）进一步增强了细胞的肿瘤抑制功能。研究人员已经证明，CITK缺失可诱导依赖p53的衰老，从而限制髓母细胞瘤的增殖。 敲低TRAF7的细胞功能抑制体外增殖和迁移 敲低TRAF7的细胞功能抑制体外增殖和迁移 02 02 研究人员通过体外实验探讨TRAF7对胶质瘤细胞增殖和迁移的影响。迁移实验显示，与对照组相比，siTRAF7组细胞迁移能力降低约60%。划痕愈合实验也表明TRAF7敲低显著抑制了细胞迁移。在24小时的时间点，siTRAF7组的伤口闭合速度略慢于对照组。然而，在Hs683细胞中，siTRAF7组在48 h后出现明显的伤口愈合障碍，伤口愈合百分比约为16.4%，而对照组为23.0% （p < 0.05）。同样，在U251细胞中，siTRAF7组的划痕愈合率为39.0%，而对照组为68.3% （p < 0.01）。 研究人员通过体外实验探讨TRAF7对胶质瘤细胞增殖和迁移的影响。迁移实验显示，与对照组相比，siTRAF7组细胞迁移能力降低约60%。划痕愈合实验也表明TRAF7敲低显著抑制了细胞迁移。在24小时的时间点，siTRAF7组的伤口闭合速度略慢于对照组。然而，在Hs683细胞中，siTRAF7组在48 h后出现明显的伤口愈合障碍，伤口愈合百分比约为16.4%，而对照组为23.0% （p < 0.05）。同样，在U251细胞中，siTRAF7组的划痕愈合率为39.0%，而对照组为68.3% （p < 0.01）。 敲低TRAF7可抑制体外细胞增殖和迁移 敲低TRAF7可抑制体外细胞增殖和迁移 与对照组相比，siTRAF7处理组的克隆形成数量减少了约50%。EdU实验结果显示，敲低TRAF7后，细胞增殖受到显著抑制。在Hs683细胞中，edu阳性细胞数量从对照组的27.33%下降到siTRAF7组的15.29% （p < 0.05）。在U251细胞系中也观察到类似的结果，进一步证明了TRAF7敲低后DNA合成的显著下降。CCK8结果显示，下调TRAF7表达后48 h，细胞活力明显下降。 与对照组相比，siTRAF7处理组的克隆形成数量减少了约50%。EdU实验结果显示，敲低TRAF7后，细胞增殖受到显著抑制。在Hs683细胞中，edu阳性细胞数量从对照组的27.33%下降到siTRAF7组的15.29% （p < 0.05）。在U251细胞系中也观察到类似的结果，进一步证明了TRAF7敲低后DNA合成的显著下降。CCK8结果显示，下调TRAF7表达后48 h，细胞活力明显下降。 结合数据，研究人员在TRAF7低表达的细胞系T98G中进行了TRAF7过表达。在T98G细胞中，克隆形成实验和迁移实验表明，与对照组相比，TRAF7过表达显著增强了T98G细胞的增殖、迁移和侵袭能力。（转化医学网360zhyx.com） 结合数据，研究人员在TRAF7低表达的细胞系T98G中进行了TRAF7过表达。在T98G细胞中，克隆形成实验和迁移实验表明，与对照组相比，TRAF7过表达显著增强了T98G细胞的增殖、迁移和侵袭能力。（转化医学网360zhyx.com） 参考资料： 参考资料： https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03363-1 https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03363-1 【关于投稿】 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！ 责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！ 微信号：zhuanhuayixue 微信号：zhuanhuayixue