替莫唑胺(Temozolomide) - 药物靶点：DNA_在研适应症：尤文肉瘤，脑恶性胶质瘤，转移性恶性黑色素瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide、3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide、3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide

+ [29]

靶点

DNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)、DNA烷化剂

治疗领域

肿瘤神经系统疾病皮肤和肌肉骨骼疾病+ [10]

在研适应症

尤文肉瘤脑恶性胶质瘤转移性恶性黑色素瘤+ [79]

非在研适应症

听神经瘤急性白血病伴有 11q23 异常的急性髓系白血病+ [108]

原研机构

Merck Sharp & Dohme Corp.

在研机构

Novartis AG

medac Gesellschaft für klinische Spezialpräparate mbH

The Children's Oncology Group Foundation, Inc.

+ [31]

非在研机构

Dartmouth-Hitchcock Medical Center

Novartis Pharmaceuticals Canada, Inc.Schering-Plough Corp.

+ [37]

权益机构

Double Bond Pharmaceutical International AB

Institut Gustave Roussy EURL

Belarusian State University

+ [1]

最高研发阶段批准上市

首次获批日期

欧盟 (1999-01-26),

星形细胞瘤多形性胶质母细胞瘤胶质瘤

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、优先审评 (中国)

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结构/序列

分子式C6H6N6O2

InChIKeyBPEGJWRSRHCHSN-UHFFFAOYSA-N

CAS号85622-93-1

关联

1,123

项与替莫唑胺相关的临床试验

NCT01777919

/ Not yet recruiting临床2期IIT

A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by
100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

开始日期2027-01-01

申办/合作机构

Universität Ulm

[+2]

NCT04373785

/ Not yet recruiting临床1/2期

A Multi-Center Pilot/Phase I and Phase II Clinical Trial of NG101m Adjuvant Therapy in Newly Diagnosed Glioblastoma Patients

The purpose of this clinical trial is to evaluate the addition of NG101m adjuvant therapy to standard of care treatment of glioblastoma multiforme. All subjects will receive NG101m capsules along with the standard treatment of temozolomide and radiation.

开始日期2027-01-01

申办/合作机构

NeuGATE Theranostics

NCT07349693

/ Not yet recruiting临床2/3期

A Randomized Trial to Assess the Efficacy and Safety of Cerebraca Wafer Plus Temozolomide Versus Temozolomide Alone in Recurrent Glioblastoma

This study is designed as a multi-center, randomized, open-label trial to evaluate the efficacy of Cerebraca Wafer in patients with recurrent glioblastoma. Cerebraca Wafer is intended for use in recurrent glioblastoma as an adjunct to surgery (followed by standard-of-care temozolomide), demonstrating potential to improve outcomes in this serious and life-threatening condition

开始日期2026-11-01

申办/合作机构

Everfront Biotech Inc.

100 项与替莫唑胺相关的临床结果

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100 项与替莫唑胺相关的转化医学

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100 项与替莫唑胺相关的专利（医药）

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11,834

项与替莫唑胺相关的文献（医药）

2026-12-31·CANCER BIOLOGY & THERAPY

Assessing progesterone receptor modulation in glioblastoma: from in vitro and animal model to a human pilot protocol

Article

作者: Cacho-Díaz, Bernardo ; Aboud, Orwa ; Guadarrama-Rangel, Carlos Fabricio ; González-Arenas, Aliesha ; Cantú-de-León, David F. ; Navarrete, Andrés Mauricio Bonilla ; Arcos-Montoya, Denisse ; Manjarrez-Marmolejo, Joaquín ; De La Fuente-Granada, Marisol ; Ordaz-Ramos, Alejandro ; Wegman-Ostrosky, Talia ; García-López, Patricia ; Díaz, Néstor Fabián ; Valdés-Rives, Silvia Anahí ; Bello-Alvarez, Claudia ; Ávila-González, Daniela ; Camacho-Arroyo, Ignacio

BACKGROUND:

Gliomas, including glioblastomas (GB) and high-grade astrocytomas (HGA), are the most common brain tumors in adults, with poor survival rates around 15 months. Hormonal factors, particularly progesterone receptor (PR) activation, promote tumor growth. Current treatment involves surgery, radiotherapy and chemotherapy (temozolomide), but survival rates remain low. Repurposing mifepristone (MF), a contraceptive drug, shows promise for GB treatment, warranting further study.

METHODS:

PR expression in U87, U251 and C6 cell lines were assessed using immunofluorescence and Western Blot. PR isoforms were quantified by densitometry. Progesterone (P4) and 5α-dihydroprogesterone (5α-DHP) synthesis were evaluated using LC/MS. MF's effect on cell viability was determined by IC₅₀ and IC₂₀ values. Its impact on non-tumoral cells and 3D glioma sphere formation was also analyzed. The effects of in situ administration of MF were assessed in vivo using a rat model with C6 glioma implants. Clinical outcomes were evaluated in GB patients receiving MF alongside standard treatment.

RESULTS:

PR was predominantly nuclear in all cell lines, with U87 showing the highest PR-B isoform levels. Only U251 synthesized 5α-DHP significantly. MF reduced viability in U251, U87 and C6 cells without affecting non-tumoral cells. Sphere formation efficiency decreased with MF treatment. In rats, MF reduced tumor volume dose-dependently. Clinically, MF improved patient survival from 165 to 588days and enhanced quality of life without severe adverse effects.

CONCLUSION:

MF effectively reduces GB cell viability, sphere formation efficacy and tumor volume. These findings support further investigation of MF as a therapeutic strategy in GB treatment.

PRÉCIS (CONDENSED ABSTRACT):

Our research highlights the critical role PR in GB progression using in vitro and in vivo models. MF, a PR modulator, effectively reduced cell viability and sphere formation in cellular assays and significantly decreased tumor volume in an in vivo study. The pilot trial demonstrated the pharmacological safety of using MF as an adjuvant in GB treatment. Patients treated with MF showed a significant increase in survival, with an 80% survival rate at 1 year compared to 0% in those who were treated with the standard treatment.

2026-12-01·JOURNAL OF MOLECULAR MEDICINE-JMM

Temozolomide increases the generation of cell heterogeneity in ERK activity in glioma cells

Article

作者: Pereira, Luiza Cherobini ; Begnini, Karine Rech ; Kraemer-Mattos, Frederico ; Marcolin, Julia Caroline ; Tórgo, Daphne ; Dos Santos, Jephesson Alex Floriano ; de Souza, Letícia Cunha Pereira ; Silva, Andrew Oliveira ; da Silva Goulart, Georgia ; Machemer, Carolina ; Lenz, Guido

Abstract:

ERK activity governs diverse cellular responses and has significant implications in cancer biology and treatment. Cellular heterogeneity is a major feature of cancer and a barrier for therapy success, allowing cancer cells to adapt and survive in challenging environments. Here, we used a genetic live-cell reporter to explore the heterogeneity of ERK signaling activity within cellular populations and colonies of glioblastoma (GB) cells. GB cells showed a wide spectrum of ERK activation levels in basal culture conditions and throughout state transitions. Treatment with the chemotherapeutic agent temozolomide increased the phenotypic heterogeneity in ERK activity within cells even in clonal populations. Using the MEK inhibitor trametinib in combination with temozolomide to homogenize ERK activity reduced cell fitness in colonies and decreased fractional killing in GB clonal cells. Our study contributes to the growing understanding of the complexity in ERK activity and dynamics, pointing out the consequences of cell-to-cell ERK phenotypic variability in fitness and therapy survival. The complexity of ERK signaling phenotypes in the context of chemotherapy treatment is shown, offering valuable insights about the intricacies of ERK signaling heterogeneity and chemotherapy treatment.

Key messages:

Heterogeneity in ERK activity in live GBM cells is high in basal culture conditions.Temozolomide alters ERK activity in GBM cells and generates phenotypic heterogeneity.Clonal populations behave heterogeneously in ERK activity, and this heterogeneity impacts fitness.Targeting the generation of ERK heterogeneity reduces fitness and fractional killing in GBM colonies.

2026-12-01·Molecular & general genetics : MGG

In vitro assessment of siRNA-mediated LRP5 silencing and temozolomide treatment in glioblastoma and brain cancer stem cells

Article

作者: Caglar, Hasan Onur ; Kucuk, Aslihan ; Biray Avci, Cigir ; Gunduz, Cumhur ; Karatas, Omer Faruk

Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of frizzled (FZD) in the WNT/β-catenin signaling pathway, recognizes Wnt ligands. This study aimed to assess the anti-cancer effects of silencing LRP5 on glioblastoma (GBM) and brain cancer stem cells (BCSCs). Additionally, the effect of temozolomide (TMZ) was also examined in these cells with suppressed LRP5 expression. LRP5 expression was silenced in U87MG, T98G, and BCSC cells using siRNA. Protein expression levels were determined by Western blotting. Cell viability after LRP5 silencing and/or TMZ treatment was evaluated using the CVDK-8 assay. Flow cytometry was used to examine apoptosis and cell cycle progression. Clonogenic, cell invasion, and wound-healing assays were used to assess colony formation, invasion, and migration, respectively. siRNA-mediated silencing reduced protein expression of LRP5 and Wnt/β-catenin target genes in GBM and BCSC cells. Furthermore, suppression of LRP5 reduced cell viability, and its combination with TMZ enhanced anti-proliferative effects. Silencing LRP5 and/or TMZ treatment caused cell cycle arrest and significantly diminished the aggressive characteristics of GBM and BCSC cells. These findings suggest that LRP5 may serve as a potential therapeutic target for treating GBM. Targeting LRP5 may enhance the effectiveness of the chemotherapy agent TMZ in GBM.

1,199

项与替莫唑胺相关的新闻（医药）

2026-05-07

·奇点网

《自然》：颠覆认知！科学家首次发现雄激素抗癌

*仅供医学专业人士阅读参考长久以来，科学家发现一个规律：在膀胱癌、结直肠癌、皮肤癌以及脑肿瘤等非生殖器官肿瘤中，男性的发病率更高，预后也更差。以最常见、最致命的原发性脑肿瘤——胶质母细胞瘤（GBM）为例，确诊患者的中位年龄在68至70岁之间，而男性患者的生存时间往往短于女性。研究者们一度将原因指向雄激素。毕竟雄激素被认为会抑制T细胞的抗肿瘤免疫功能，从而为肿瘤的生长“保驾护航”。在前列腺癌、膀胱癌等肿瘤中，阻断雄激素受体信号确实能增强免疫检查点抑制剂的效果。于是，有研究人员推测，对GBM患者施行雄激素剥夺，或许同样有益。然而，由克利夫兰诊所Justin D. Lathia领衔的研究团队，今天发表于《自然》杂志的最新研究，对这一逻辑提出了正面挑战[1]。Lathia团队发现，雄激素在脑肿瘤中扮演的角色，竟然与它在身体其他部位肿瘤中的角色截然相反。在脑肿瘤中，它不是“帮凶”，而是“守卫”。简单来说，雄激素缺失会放大脑内的神经炎症反应，进而异常激活下丘脑-垂体-肾上腺（HPA）轴，最终导致全身性免疫抑制，加速脑肿瘤的进展。Lathia团队分析了58名高级别胶质瘤患者的肿瘤活检数据，发现50岁以上的男性患者肿瘤内T细胞数量显著低于50岁以下的男性，而这一年龄依赖性规律在女性患者中并不存在。这与男性随年龄增长睾酮水平下降的生理现象高度吻合，暗示雄激素减少可能削弱了脑肿瘤免疫监视。为了在动物模型中验证这一想法，Lathia团队对小鼠进行手术去势后植入颅内GBM肿瘤，结果令人震惊：去势小鼠的生存期显著缩短，肿瘤体积也更大。更让人意外的是，这种效应具有部位特异性而非肿瘤类型特异性。无论是膀胱癌细胞还是黑色素瘤细胞，只要植入颅内，去势后的小鼠同样活得更短；而将同一批GBM细胞皮下注射至躯干，去势反而延缓了肿瘤生长。此外，对于GBM小鼠而言，雄激素受体拮抗剂恩扎鲁胺处理会缩短生存期；相反，给去势小鼠补充外源性睾酮，则能逆转生存期的缩短，甚至对睾酮正常的小鼠额外给药，生存期也进一步延长。以上基于小鼠的研究说明，雄激素是通过雄激素受体信号发挥脑肿瘤保护作用的。为了检验上述发现的临床意义，Lathia团队分析了SEER-Medicare数据库的临床数据，发现同时接受睾酮补充和替莫唑胺化疗的GBM男性患者（n=61），中位总生存期为16个月，比仅接受替莫唑胺的患者（n=1272，中位12个月）显著延长，死亡风险降低约34%至38%。那么，雄激素究竟如何在脑内发挥这种保护作用呢？Lathia团队发现，在去势小鼠的脑肿瘤中，肿瘤细胞的增殖速率没有变化，但凋亡标志物的水平下降，提示是肿瘤细胞死得更少而非长得更快，这把矛头指向了免疫清除能力的下降。如果用缺乏T细胞和B细胞的小鼠重复实验，会发现去势不再影响生存期，证明这一效应依赖于适应性免疫。围绕GBM小鼠的免疫分析结果表明，去势后，不论是肿瘤浸润T细胞，还是外周淋巴结和脾脏中的T细胞，分泌IFNγ和TNF等抗肿瘤细胞因子的能力均大幅下降；显然，去势导致了系统性的T细胞功能障碍。对于GBM小鼠而言，雄激素缺失为何会对免疫系统产生如此之大的负面作用呢？Lathia团队的目光落在了糖皮质激素上。他们发现去势小鼠血清中的皮质酮（活性糖皮质激素）显著升高，且这种升高在脑肿瘤存在时更为突出。要知道，糖皮质激素可是T细胞功能的抑制剂。如果用糖皮质激素受体拮抗剂米非司酮阻断这一信号，则能显著延长去势GBM小鼠的生存期，并恢复T细胞的细胞因子分泌能力。从机制上来看，雄激素缺失会导致小胶质细胞炎症小体过度激活，促炎细胞因子IL-1β/TNF大量表达和释放；下丘脑中增强的促炎细胞因子信号，会导致下丘脑-垂体-肾上腺（HPA）轴被异常过度激活，这使得下丘脑神经细胞活性增加，并促使垂体大量分泌促肾上腺皮质激素；异常升高的促肾上腺皮质激素进入血液循环后，会刺激肾上腺，导致具有强效免疫抑制作用的糖皮质激素（尤其是活性形式的皮质酮）在血清中的水平显著增加；激增的糖皮质激素主要作用于肿瘤微环境中髓系细胞（如巨噬细胞）上的糖皮质激素受体，打造免疫抑制微环境，进而引发全身性的T细胞功能障碍。总的来说，雄激素在脑肿瘤中扮演着一种“肿瘤抑制因子”的角色。它的缺失会引发“神经炎症放大→HPA轴亢进→糖皮质激素激增→髓系细胞介导的T细胞功能耗竭”这一连串由肿瘤外在机制驱动的链式反应，最终通过破坏免疫系统的抗癌能力促进了肿瘤的进展。显而易见的是，这个研究颠覆了此前将雄激素一概视为促肿瘤因子的传统认知，首次在机制层面阐明了雄激素在脑肿瘤中发挥免疫保护作用，而非免疫抑制作用角色的生物学原理。在临床层面，它为老年男性GBM患者的睾酮补充疗法提供了生物学依据，同时也提醒临床医生警惕针对脑肿瘤患者盲目套用雄激素剥夺策略的潜在风险——特别是在脑转移患者中。欢迎大家关注我们在小宇宙上的播客栏目——药研片语，欢迎大家前去收听并与我们交流~参考文献：[1].Lee, J., Chung, YM., Silver, D.J. et al. Androgen loss accelerates brain tumour growth via HPA axis activation. Nature (2026). https://doi.org/10.1038/s41586-026-10451-5本文作者丨BioTalker

2026-05-06

·国际干细胞与免疫细胞研究

75%控病率+60%两年无复发！2026 DC疫苗交出重磅答卷，覆盖肺癌、胃癌、肝癌、脑瘤等

点击蓝字关注我们树突状细胞（DC）是人体功能最强的抗原呈递细胞，也是重要的免疫“哨兵”，在抗肿瘤免疫应答中居于核心地位，能够激活全身免疫、精准识别并清除癌细胞。依托这一机制研发的新抗原个性化DC疫苗，已成为肿瘤免疫治疗领域极具潜力的前沿方向。目前，全球多项临床研究均已证实：新抗原DC疫苗安全性良好、临床应用可行，在多种实体瘤中表现出稳定的抗肿瘤作用，也为晚期肿瘤患者及术后防复发人群开辟了全新治疗思路。为帮助大家了解前沿抗癌新方案、树立治疗信心，下面我们就系统梳理新抗原DC疫苗在实体瘤领域的最新临床研究进展与技术突破！晚期肺癌多线失败后，这款DC疫苗让转移灶“消退”，疾病控制率高达75% 一项针对晚期肺癌的单臂试点研究（NCT02956551），旨在研究个性化新肽脉冲树突状细胞疫苗（Neo-DCVac）的安全性和有效性。该研究纳入了12例多线标准治疗失败的复发性晚期肺癌患者，每位患者均接受了自体树突状细胞（DC）疫苗，该疫苗以12-30种新肽进行脉冲处理，该研究取得了令人鼓舞的结果。研究数据显示：客观缓解率（ORR）达25%，疾病控制率（DCR）高达75%（详见下图d）；中位无进展生存期（PFS）5.5个月（95%CI：1.9-9.2，详见下图b），中位总生存期（OS）7.9个月（95%CI：5.9-10.0，详见下图c）。12例患者中，有6例（50%）靶病灶出现缩小。 ▲图源“Signal Transduct Target Ther”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除研究中有两例典型患者表现尤为突出。第一例为15号广泛期小细胞肺癌男性患者，该患者多线常规治疗失败后，接受Neo-DCVac疫苗干预。完成5剂疫苗治疗后，病情达到稳定（SD），靶病灶较基线最大缩小15%，疾病稳定时长接近一年。另一例极具临床参考价值的是17号广泛转移性肺腺癌男性患者，转移累及骨骼、盆腔、肾上腺及下腔静脉淋巴结。患者在含纳武利尤单抗（PD-1抑制剂）的三线方案治疗失败后，入组接受Neo-DCVac疫苗治疗（图5a）。完成5剂治疗后，转移性淋巴结近乎消退，肾上腺、盆腔转移灶也持续缩小，整体靶病灶缩小幅度达29%（图5b）。免疫检测结果显示患者接种疫苗后的外周血单个核细胞（PBMC），对两种突变新抗原肽的特异性应答，显著强于野生型肽段，充分印证了这款个性化DC疫苗在抗肿瘤中的确切作用。 ▲图源“Signal Transduct Target Ther”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 13例患者全部存活！肝癌术后DC疫苗防复发效果显著，2年无复发率达60% 2024年ASCO大会报道了一项肝细胞癌术后辅助治疗试点试验（NCT04147078），该试验旨在评估个性化新抗原肽脉冲自体树突状细胞疫苗（Neo-DCVac-02）在局部晚期实体瘤术后患者中的安全性与有效性。研究纳入13例肝细胞癌（HCC）术后患者，结果证实，Neo-DCVac-02安全性良好且耐受性佳，能显著延迟患者肝癌复发：1年无复发生存率达84.6%，2年无复发生存率为60%，且所有患者均存活。进一步分析显示，免疫反应较强患者的中位无复发生存期（尚未达到）显著长于免疫反应较弱患者（17.6个月，P=0.003）。综上，Neo-DCVac-02不仅安全耐受，还能诱导持久的抗原特异性淋巴细胞免疫反应，这种免疫应答可能是延迟肝细胞癌术后复发的关键。全球首例！DC疫苗联合PD-1抑制剂，助胃癌患者实现病灶完全消退国际权威《Nature》子刊刊发重磅病例研究，报道了Neo-MoDC疫苗治疗晚期胃癌的突破性案例。这也是全球已知首例经Neo-MoDC联合PD-1治疗后，肿瘤实现完全消退且长期维持的胃癌病例，具有里程碑意义。该患者确诊为晚期（IV期，Bormann III型）转移性胃癌，既往接受过D2根治性远端胃切除术、FOLFOX治疗等，但病情仍然进展，且已出现腹膜及淋巴结转移。此时临床已无其他适合的治疗方案可选，加之其符合入组标准，抱着最后一丝希望，该患者参加了Neo-MoDC临床试验（NCT03185429）。入组后接受Neo-MoDC联合免疫检查点抑制剂（PD-1）治疗。结果显示：该患者在首轮纳武单抗治疗后5天，血清肿瘤标志物CA125水平从596U/ml，迅速下降至64U/ml，这也意味着该患者肿瘤进展得到控制！更为惊喜的是，2周后患者恶性腹水症状也消失。初次接种疫苗后的第231天，PET显示该患者右侧卵巢病灶近乎完全消退。联合治疗第389天，CT显示患者卵巢种植转移完全消失（详见图3）。幸运的是，截至2021年10月复查CT显示，完全消退持续25个月之久！ ▼该患者治疗期间目标肿瘤病变的代表性图像 ▲图源“NPJ”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：黄色箭头代表目标肿瘤病变；蓝色箭头代表肿瘤病变完全消退。打破二十年治疗僵局DC疫苗Ⅲ期临床显著延长胶质母细胞瘤患者生存期，一年生存率高达54.1% 过去数十年研究证实，负载肿瘤裂解物的树突状细胞（DC）疗法，用于胶质母细胞瘤（GBM）治疗，整体安全性可控、毒性耐受良好。《转化医学杂志》公布了自体树突状细胞疫苗DCVax®-L治疗初诊胶质母细胞瘤的大型Ⅲ期临床试验（NCT00045968）首批生存数据。该研究共纳入331例胶质母细胞瘤患者，采用负载自体肿瘤裂解物的DC疫苗DCVax-L，联合标准治疗药物替莫唑胺开展干预，并将新诊断的胶质母细胞瘤（nGBM）、复发性胶质母细胞瘤（rGBM）患者，与同期接受常规标准治疗的匹配外部队列进行对照分析。结果显示：接受DCVax-L治疗的新诊断的胶质母细胞瘤（nGBM）患者的中位总生存期（OS）为19.3个月，而同期接受标准治疗（SOC）的匹配外部对照组患者的中位OS为16.5个月（详见下图A）。DCVax-L使nGBM队列（n=232）的4年生存率提高至15.7%，显著高于对照组的9.9%。 ▲图源“JAMA Oncol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除在复发性胶质母细胞瘤（rGBM）队列（n= 64）中，与对照组相比，DCVax-L组的中位总生存期（mOS）显著延长，分别为13.2个月（95% CI，9.7-16.8个月） vs 7.8个月（95% CI，7.2-8.2个月，详见下图）。 ▲图源“JAMA Oncol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除总之，这项试验是近20年来，首个成功延长初诊胶质母细胞瘤患者总生存期的大型 Ⅲ 期临床研究，为胶质母细胞瘤的治疗开辟了全新方向与希望。小编寄语癌症疫苗历经数十载的发展，逐渐从实验室转向临床研究阶段。值得欣慰的是，不断有DC、mRN等新款疫苗涌现，一次次地突破技术壁垒，在癌症的预防、治疗领域不断寻求新的突破，小编也期望随着癌症疫苗的不断优化，未来可以创造出更多的抗癌奇迹，让更多的高危人群及癌症患者获益！想寻求癌症疫苗等国内外抗癌新技术帮助的病友，可扫文末二维码，将治疗经历、近期病理报告等，提交至国际干细胞与免疫细胞研究医学部，进行初步评估。参考资料 [1]Ding Z,et al.Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer. Signal Transduct Target Ther. 2021 Jan 20;6(1):26. https://pmc.ncbi.nlm.nih.gov/articles/PMC7817684/ [2]Wu Q,et al.A pilot trial of personalized neoantigen pulsed autologous dendritic cell vaccine as adjuvant treatment in hepatocellular carcinoma[J]. 2024. https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.e16264 [3]Guo Z,et al.Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer. NPJ Precis Oncol. 2022 Jun 3;6(1):34. https://pmc.ncbi.nlm.nih.gov/articles/PMC9166775/ [4]Liau LM,et al.Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial. JAMA Oncol. 2023 Jan 1;9(1):112-121. https://pmc.ncbi.nlm.nih.gov/articles/PMC9673026/ 本文为“国际干细胞与免疫细胞研究”原创，转载需授权干细胞与免疫细胞研究入群免费领取抗癌细胞资讯｜新技术｜新药研发｜权威专家资料求分享求收藏求点击求在看

疫苗临床结果临床研究

2026-05-06

·今日头条

市二医（金阳医院）召开肿瘤科GCP项目——KH617临床试验项目启动会

为推动神经肿瘤领域前沿药物临床试验落地，4月30日，市二医（金阳医院）召开“注射用KH617联合替莫唑胺治疗复发性胶质母细胞瘤Ⅱ期临床试验”启动会，这是医院继GH56、SM-1两项临床试验项目后开展的第三项临床试验，为复发性胶质母细胞瘤患者提供更多治疗选择。首都医科大学附属北京天坛医院肿瘤综合治疗中心副主任医师康庄、市二医（金阳医院）肿瘤科、GCP办公室、病理科、影像科等相关科室骨干及项目申办方代表共同参会，会议由肿瘤科负责人杨黎主持。首都医科大学附属北京天坛医院肿瘤综合治疗中心副主任医师康庄长期深耕神经系统肿瘤综合治疗与新药临床试验，参与完成I-Ⅲ期临床研究40余项，对KH617药物研发及复发性胶质母细胞瘤诊疗有着深厚经验。她作为该项目核心研究者强调，KH617作为新型抗肿瘤药物，前期I期研究已显示其能有效抑制肿瘤生长，并具有良好地穿透血脑屏障的能力，为复发患者提供了新的潜在治疗选择。本次Ⅱ期多中心研究旨在进一步验证其联合替莫唑胺的有效性与安全性，为临床应用提供高级别证据。她希望两地团队紧密协作，严把研究质量关，共同推动项目顺利开展，为攻克神经肿瘤难题贡献力量。随后，申办方对试验项目入排标准、用药流程等进行讲解，对相关协作科室及GCP人员提出的问题进行了解答，为项目细节做出更多详细解释。最后，肿瘤科负责人杨黎在总结中提到，复发性胶质母细胞瘤作为临床难治性恶性肿瘤，现有治疗手段有限，患者预后亟待改善。本次KH617项目启动，是医院承接高水平多中心临床研究、提升神经肿瘤诊疗与科研能力的重要契机，科室将严格遵循GCP规范，高标准、高质量推进研究实施，为贵州乃至全国患者搭建前沿治疗平台。本次启动会的顺利召开，标志着KH617临床试验项目在医院正式落地实施，为复发性胶质母细胞瘤患者带来了新的治疗希望，也进一步深化了京黔两地在神经肿瘤领域的科研合作。未来，医院将以此为契机，持续提升临床研究能力，推动更多前沿药物与技术惠及广大肿瘤患者。

100 项与替莫唑胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06067	替莫唑胺	L01AX03	DB00853

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
尤文肉瘤	日本	Ohara Pharmaceutical Co., Ltd.	2019-02-21
尤文肉瘤	日本	MSD KK (Tokyo)	2019-02-21
脑恶性胶质瘤	欧盟	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	冰岛	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	列支敦士登	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	挪威	Teva Pharmaceuticals Europe BV	2010-01-28
转移性恶性黑色素瘤	澳大利亚	Merck Sharp & Dohme (Australia) Pty Ltd.	2009-11-13
胶质母细胞瘤	中国	江苏天士力帝益药业有限公司	2004-04-30
星形细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	挪威	Merck Sharp & Dohme BV	1999-01-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
神经母细胞瘤	申请上市	欧盟	ORPHELIA Pharma SAS	2024-11-14
胶质母细胞瘤，IDH野生型	临床3期	-	NRG Oncology	2026-06-08
子宫平滑肌肉瘤	临床3期	美国	Alliance for Clinical Trials in Oncology	2022-03-30
脑干胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
脑干胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
小儿小脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26

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临床结果

适应症

分期

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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


NCT03334305 (ACTION, CTgov)	临床1期	高级别胶质瘤	18	Td vaccine+TTRNA-DC vaccines with GM-CSF+Dose-intensified TMZ+TTRNA-xALT (Group A)	壓齋遞鹹願觸窪製網醖 = 餘繭窪鹽襯餘選顧襯顧壓艱鑰鬱願簾窪壓願獵 (網築壓構網醖鏇獵艱齋, 鏇襯顧淵繭糧窪衊鏇構 ~ 繭窪願糧簾簾膚範壓憲) 更多	-	2026-04-23
				Autologous Hematopoietic Stem cells (HSCs)+TTRNA-DC vaccines with GM-CSF+Dose-intensified TMZ+TTRNA-xALT (Group B)	獵網餘範獵廠鏇窪築齋(鏇艱鬱衊窪夢衊獵選淵) = 顧範鑰製願積廠糧構遞觸網鏇願糧選淵選壓淵 (窪構餘醖鬱簾積積齋鹹, 壓鏇鏇鏇夢襯餘築蓋鹽 ~ 憲鏇窪顧廠餘鹽獵獵觸) 更多
NCT04457284 (AACR2026)	临床2期	转移性结直肠癌 MSH2 \| MSI \| TMB	16	TMZ+CDDP+nivolumab	遞鑰選鹹淵淵蓋鹹壓製(築蓋獵顧製齋遞憲襯鹹) = 夢遞蓋餘顧蓋選膚齋鏇構顧齋醖襯簾築遞醖鏇 (網獵鏇鏇築鏇壓夢製積 )	积极	2026-04-19
NCT02595424 (ECOG-ACRIN EA2142, CTgov)	临床2期	高分化胰腺内分泌肿瘤 \| 胃神经内分泌肿瘤 \| 神经内分泌癌	67	Laboratory Biomarker Analysis+Temozolomide+Capecitabine (Arm A (Capecitabine, Temozolomide))	艱餘鏇製蓋壓窪淵夢積(遞鬱壓夢蓋夢製壓夢糧) = 築顧顧醖齋齋獵觸襯簾遞鏇選艱齋廠選膚艱壓 (製鑰餘蓋蓋艱憲範憲鑰, 醖觸鹹鑰壓顧繭齋鬱醖 ~ 遞鹹憲衊繭艱壓艱夢餘) 更多	-	2026-04-08
				Laboratory Biomarker Analysis+Etoposide+Carboplatin+cisplatin (Arm B (Cisplatin, Carboplatin, Etoposide))	艱餘鏇製蓋壓窪淵夢積(遞鬱壓夢蓋夢製壓夢糧) = 獵選艱網鏇繭築夢選觸遞鏇選艱齋廠選膚艱壓 (製鑰餘蓋蓋艱憲範憲鑰, 糧醖構製鬱憲蓋願鑰鬱 ~ 簾鏇齋襯觸餘構衊窪選) 更多
NCT05432791 (Alliance A092104, CTgov)	临床2/3期	子宫平滑肌肉瘤	74	Multigated Acquisition Scan+Olaparib+Temozolomide (Arm 1 (Olaparib, Temozolomide))	獵壓範築夢鏇構鑰簾遞(壓壓憲襯願膚繭艱艱鹹) = 網構壓範遞鑰壓襯襯膚鑰願膚衊醖醖壓糧遞襯 (蓋淵鏇膚餘觸糧衊構衊, 糧憲網顧鬱製艱網憲窪 ~ 構願鏇築積遞窪襯膚願) 更多	-	2026-04-08
				Multigated Acquisition Scan+Trabectedin+Pazopanib (Arm 2 (Trabectedin, Pazopanib))	獵壓範築夢鏇構鑰簾遞(壓壓憲襯願膚繭艱艱鹹) = 衊積蓋願膚膚鹽襯鹹鑰鑰願膚衊醖醖壓糧遞襯 (蓋淵鏇膚餘觸糧衊構衊, 憲壓壓觸膚憲淵製衊網 ~ 蓋窪窪糧廠構夢築糧廠) 更多
NCT03197506 (CTgov)	临床2期	多形性胶质母细胞瘤	52	temozolomide+pembrolizumab (Group 1 Dose Level 1 Cohort 1)	廠範壓鏇網鹽積網鹹鹹 = 糧積遞觸範築糧艱淵衊淵鹹鬱憲觸製蓋餘艱顧 (構構鑰糧顧襯網衊願齋, 鹹鹽積鑰膚網醖餘夢築 ~ 選範獵鹽範網餘糧選襯) 更多	-	2026-03-25
				temozolomide+pembrolizumab (Group 1 Dose Level 1 Cohort 2)	廠範壓鏇網鹽積網鹹鹹 = 淵窪膚衊繭夢積簾積壓淵鹹鬱憲觸製蓋餘艱顧 (構構鑰糧顧襯網衊願齋, 簾艱壓遞膚憲鹽鹹鹽繭 ~ 蓋餘遞顧觸鹽願襯網網) 更多
ESMO_SRC2026	N/A	尤文肉瘤	20	Temozolomide 100 mg/m² orally + irinotecan 40 mg/m² intravenously	齋鑰構選鬱窪鏇鏇憲壓(鹹鹹積繭鹹築衊願壓窪) = 築網膚廠壓窪淵壓艱襯醖糧獵範憲齋鑰鏇淵廠 (鬱選夢積鑰網襯網襯繭 ) 更多	积极	2026-03-09
ESMO_SRC2026	N/A	琥珀酸脱氢酶缺陷型胃肠道间质瘤	19	imatinib	齋廠範艱簾糧窪簾襯艱(築選鑰鹽夢糧願構獵築) = 壓構膚築構獵積鏇積製鑰蓋鹽襯遞膚獵簾觸鹹 (積鏇製糧齋膚糧鹽網範, 50.7 ~ NR)	积极	2026-03-09
				sunitinib	鹽製鹽鏇繭觸網餘鏇膚(簾鬱顧艱顧網遞蓋鹹窪) = 齋艱衊夢憲窪鏇製鹹範鬱鹹觸鏇艱願艱遞衊獵 (選構醖廠選網製鏇選鑰 )
NCT03519412 (ARETHUSA, CTgov)	临床2期	转移性结直肠癌	107	pembrolizumab (MMR-deficient (MMRd))	窪願範網鬱簾齋鏇遞齋 = 餘鹽鏇壓簾夢窪遞襯鏇衊遞憲壓壓獵鹹鹽餘窪 (鹹遞鬱憲範蓋鏇製鬱醖, 衊鏇繭衊齋糧構鏇艱廠 ~ 鏇網鬱遞壓艱鬱壓繭製) 更多	-	2026-03-03
				temozolomide+pembrolizumab (MMR-proficient (MMRp))	構廠網遞憲壓夢獵鑰觸 = 鏇構鹹顧鹽鹽鹽選簾範憲遞鏇鑰憲窪範齋廠淵 (繭膚齋鬱齋餘鬱膚選遞, 餘糧鬱網夢齋繭選廠蓋 ~ 獵願鑰廠觸衊遞齋築鬱) 更多
NCT04200443 (Pubmed \| Lancet Oncol)	临床2期	平滑肌肉瘤 \| 软组织肉瘤	72	Cabozantinib 40 mgTemozolomide 40 mg + Cabozantinib 40 mgTemozolomide	蓋顧鏇夢遞積鹹夢醖淵(窪蓋鏇淵鹽簾鑰鏇蓋獵) = 顧簾憲構製壓鹽觸醖醖艱襯衊獵艱膚窪醖糧膚 (壓選艱鑰鏇製選齋齋壓 ) 更多	积极	2026-02-01
				Temozolomide (Cohort 1)	窪獵鹽築觸鑰築積醖襯(願鹹網築構醖築鹽齋窪) = 齋鬱艱鹽鹽築膚顧範鬱窪憲遞顧選築顧選廠遞 (積蓋積網窪鏇艱鏇製構 ) 更多
NCT03794349 (Phase 1 study \| ANBL1821, CTgov)	临床2期	复发性神经母细胞瘤 \| 难治性神经母细胞瘤 \| 高风险神经母细胞瘤	94	Dinutuximab+Temozolomide+Sargramostim+Irinotecan Hydrochloride (Regimen A (Chemotherapy, Dinutuximab, Sargramostim))	襯獵淵鏇夢製蓋醖構鹽 = 積艱衊觸膚獵選遞窪鬱繭製觸鑰窪憲鬱鏇鏇廠 (積糧鏇糧艱憲鏇夢衊廠, 願齋淵製膚憲獵膚襯觸 ~ 範鑰願鹹齋選艱鹽淵願) 更多	-	2026-01-21
				Dinutuximab+Temozolomide+Sargramostim+Irinotecan Hydrochloride+Eflornithine Hydrochloride (Regimen B (Eflornithine, Chemotherapy, Dinutuximab))	襯獵淵鏇夢製蓋醖構鹽 = 遞願襯顧獵範壓襯鬱窪繭製觸鑰窪憲鬱鏇鏇廠 (積糧鏇糧艱憲鏇夢衊廠, 願淵壓製鹹艱夢鑰糧鏇 ~ 鹹襯憲鹹鏇廠鹹夢鏇壓) 更多