更新于：2024-11-01

Ganglioglioma

节细胞神经胶质瘤

更新于：2024-11-01

基本信息

别名

Ganglioglioma、Ganglioglioma (disorder)、Ganglioglioma (morphologic abnormality)

+ [13]

简介

Rare indolent tumors comprised of neoplastic glial and neuronal cells which occur primarily in children and young adults. Benign lesions tend to be associated with long survival unless the tumor degenerates into a histologically malignant form. They tend to occur in the optic nerve and white matter of the brain and spinal cord.

关联

项与节细胞神经胶质瘤相关的药物

Vebreltinib

伯瑞替尼

靶点

c-Met

作用机制

c-Met抑制剂

在研机构

Apollomics, Inc. (United States) [+2]

原研机构

浙江冠科美博生物科技有限公司

在研适应症

IDH突变星形细胞瘤 [+18]

非在研适应症

c-Met阳性非小细胞肺癌 [+4]

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2023-11-14

Dabrafenib Mesylate

甲磺酸达拉非尼

靶点

BRAF x CRAF

作用机制

BRAF抑制剂 [+1]

在研机构

Novartis Pharmaceuticals Corp. [+10]

原研机构

GSK Plc

在研适应症

BRAF 基因突变的毛细胞白血病 [+39]

非在研适应症

成釉细胞瘤 [+9]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2013-05-29

Trametinib dimethyl sulfoxide

二甲基亚砜曲美替尼

靶点

MEK1 x MEK2

作用机制

MEK1抑制剂 [+1]

在研机构

Novartis Europharm Ltd. [+11]

原研机构

GSK Plc

在研适应症

低级神经胶质瘤 [+110]

非在研适应症

肺腺癌 [+34]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2013-05-29

项与节细胞神经胶质瘤相关的临床试验

NCT03919071 / Recruiting临床2期IIT

A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)

This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

开始日期2020-02-20

申办/合作机构

National Cancer Institute

NCT03975829 / Active, not recruiting临床4期

An Open Label, Multi-center Roll-over Study to Assess Long-term Effect in Pediatric Patients Treated With Tafinlar (Dabrafenib) and/or Mekinist (Trametinib)

A roll-over study to assess long-term effect in pediatric patients treated with dabrafenib and/or trametinib.

开始日期2019-11-04

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT04065776 / RecruitingN/AIIT

A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma

Low-grade gliomas (LGGs) are the most common brain tumors in children, and a subset of these tumors are treated definitively with focal radiation therapy (RT). These patients often survive for many years after receiving RT and experience late deficits in memory. Verbal recall is an important measure of memory and is associated with other important functional outcomes, such as problem-solving, independence of every-day functioning, and quality of life. Decline in memory, as measured by verbal recall, is associated with RT dose to the hippocampi. Therefore, this phase II study investigates the feasibility of reducing RT doses to the hippocampi (i.e., hippocampal avoidance [HA]) by using proton therapy for midline or suprasellar LGGs.
Primary Objective:
To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs. Feasibility will be established if 70% of plans meet the first or second dose constraints shown below.
First priority RT dose constraints for bilateral hippocampi: volume receiving 40 CGE (V40CGE) ≤ 25%, dose to 100% of Hippocampus (D100%) ≤ 5CGE.
Second priority RT dose constraints for bilateral hippocampi: V40CGE ≤ 35%, D100% ≤ 10 CGE.
Secondary Objectives:
To estimate the 3-year event-free-survival (EFS) for LGGs treated with HA.
To estimate the change in California Verbal Learning Test short-term delay (CVLT-SD) from baseline to 3 years and from baseline to 5 years
To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that: (1) meet first priority RT dose constraints, (2) meet second priority RT dose constraints but not first priority RT dose constraints, and (3) that did not meet either first or second RT priority dose constraints
Exploratory Objectives:
To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery, including gold standard measures shown in the published studies to be sensitive to attention, memory processing speed and executive function that will afford comparison to historical controls.
To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi.
To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography (MET-PET) uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology.
To investigate the effect of BRAF alteration, tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner.
To investigate whether the methylation profiles of LGGs differ by tumor location (thalamic/midbrain vs. hypothalamic/optic pathway vs. others) and histologies (pilocytic astrocytoma vs. diffuse astrocytoma vs. others), which, in conjunction with specific genetic alterations, may stratify patients into different subgroups and highlight different therapeutic targets.
To record longitudinal measures of circulating tumor DNA (ctDNA) in plasma and correlate these measures with radiographic evidence of disease progression.
To bank formalin-fixed, paraffin-embedded (FFPE)/frozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol.
To quantify and characterize tumor infiltrating lymphocytes (TILs) and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment.
To estimate the cumulative incidence of endocrine deficiencies, vision loss, hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy.

开始日期2019-08-28

申办/合作机构

St. Jude Children's Research Hospital, Inc.

100 项与节细胞神经胶质瘤相关的临床结果

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100 项与节细胞神经胶质瘤相关的转化医学

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0 项与节细胞神经胶质瘤相关的专利（医药）

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1,629

项与节细胞神经胶质瘤相关的文献（医药）

2024-12-31·OncoImmunology

Transcriptomics-based characterization of the immuno-stromal microenvironment in pediatric low-grade glioma

Article

作者: Schüller, Ulrich ; Bockmayr, Michael ; Spohn, Michael ; Körner, Meik

Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.

2024-11-01·International Journal of Surgery Case Reports

A ganglioglioma versus a schwannoma: Which is in the sacral spine?

Article

作者: Younes, Philippe ; Fahed, Elie ; Abadjian, Gerard ; Msheik, Ali ; Sebaaly, Delivrance

INTRODUCTION AND IMPORTANCESacral spinal gangliogliomas, rare WHO grade I tumors, present a surgical challenge due to their proximity to critical nerve roots. Symptoms often include lower back pain, sciatica, and bladder dysfunction. Diagnosis is confirmed through MRI and biopsy, with surgical resection being the primary treatment.CASE PRESENTATIONA 66-year-old woman presented with left lower limb pain and weakness. MRI showed an intradural lesion at the left S1 root. She underwent surgery, resulting in near-total tumor resection. Postoperatively, she was pain-free and ambulatory. Pathology confirmed a ganglioglioma.CLINICAL DISCUSSIONInitially suspected as a disc herniation, MRI indicated a schwannoma-like lesion, but surgery and pathology revealed a ganglioglioma. Total resection was challenging due to the tumor's neural adherence. Radiotherapy and chemotherapy are generally not used for low-grade gangliogliomas.CONCLUSIONTreating sacral spinal gangliogliomas requires precise surgery and a multidisciplinary approach. Accurate diagnosis and careful planning are essential for minimizing neurological risks and improving patient outcomes. Continued research is crucial for advancing treatment strategies.

2024-11-01·Cancer Genetics

Focal cortical dysplasia type IIIb associated with a KRAS-mutant ganglioglioma

Article

作者: Roberts, Jennifer ; Gener, Melissa ; Kats, Alexander ; Orr, Brent A ; Zinkus, Timothy ; Repnikova, Elena A ; Zhang, Lei

项与节细胞神经胶质瘤相关的新闻（医药）

2024-06-17

·drugs

Epilepsy Surgery for Neuroglial Tumors Shows Good Long-Term Outcomes

MONDAY, June 17, 2024 -- Patients with neuroglial tumors are ideal epilepsy surgical candidates, with good long-term outcomes observed, according to a study published online May 22 in Frontiers in Neurology . Attila Rácz, M.D., Ph.D., from the University Hospital Bonn in Germany, and colleagues evaluated long-term outcomes and potential influencing factors among 107 patients who underwent surgery for neuroglial tumors (2001 to 2020) at a single institution. The researchers found that 75 percent of the patients who underwent surgery achieved complete freedom from seizures at 12 months and 56 percent achieved complete freedom from seizures at the last follow-up visit (70.4 months; median: 40 months). For both 12-month follow-up outcomes and the longest available outcomes, completeness of resection was a crucial factor, while there was no consistent impact on postsurgical outcomes for lobar tumor localization, histology (ganglioglioma versus dysembryoplastic neuroepithelial tumor), history of bilateral tonic-clonic seizures prior to surgery, invasive diagnostics, side of surgery (dominant versus nondominant hemisphere), age at epilepsy onset, age at surgery, or epilepsy duration. Patients who underwent lesionectomy and lesionectomy with hippocampal resection showed similar outcomes. "Neuroglial tumors present as excellent surgical substrates in treating structural epilepsy," the authors write. "To achieve an optimal postsurgical outcome, a complete lesion resection should be pursued whenever possible." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

临床结果

2022-11-04

·BiG生物创新社

癌症治疗过程的双向间谍--巨噬细胞

12月21-22日，上海大咖带队，新秀集结！以创新利刃，破内卷之局前言肿瘤相关巨噬细胞是肿瘤微环境的重要组成部分，在血管生成、细胞外基质重塑、癌细胞增殖、转移和免疫抑制的协调以及化疗药物和检查点阻断免疫治疗的耐药性方面发挥作用。当被适当激活时，巨噬细胞可以介导癌细胞的吞噬作用和肿瘤细胞毒性的杀伤，并与先天性和适应性免疫系统的组分进行有效的双向相互作用。因此，它们已成为癌症治疗的治疗靶点。巨噬细胞靶向策略包括参与肿瘤促进性骨髓细胞募集和极化的细胞因子以及趋化因子抑制剂，和其抗肿瘤原性和免疫刺激功能的激活剂。早期的临床试验表明，靶向骨髓细胞功能的负调节因子（检查点）确实具有抗肿瘤潜力。最后，鉴于骨髓单核细胞不断募集到肿瘤组织中，随着嵌合抗原受体效应细胞的发展，巨噬细胞是细胞治疗的候选者。以巨噬细胞为中心的治疗策略有可能补充和协同肿瘤学治疗中现有的方法。作者 | 北夔01TAM 多样性和预后长期以来，人们一直认为TAM起源于骨髓（BM）衍生的单核细胞前体，充满肿瘤隔室。在许多小鼠模型中，大多数TAM确实来自单核细胞前体。然而，发现在稳态条件下，组织驻留巨噬细胞（TRM）起源于胚胎生命种子器官的胚胎前体。由此便提出了一个问题，即除了BM衍生的前体外，TRM还可能维持TAM水平。在胰腺癌小鼠模型中，TRM局部增殖并获得纤维化，促进促腺皮质增生反应，这是胰腺导管腺癌的典型特征。此外，在小鼠卵巢癌中，在网膜中的自我更新的CD163 Tim4巨噬细胞种群通过产生癌症干细胞来促进转移性扩散。高巨噬细胞浸润与大多数人类肿瘤的预后不良有关。但一个值得注意的例外是CRC，其中TAM预测更好的预后，特别是对于对 5-氟尿嘧啶辅助治疗有反应的 III 期 CRC 患者，在CRC的肝转移中，具有不同形态和分子指纹的TAM共存并与临床病理变量相关，因此与小TAM相比，大的TAM与较差的存活率相关。在乳腺癌中，冠状结构由冠状垂死脂肪细胞周围的巨噬细胞组成，支持肿瘤进展并具有预后潜力。图1：TAM的促肿瘤功能和免疫抑制活性02传统癌症治疗中的 TAM巨噬细胞在不同抗癌方式的活性中具有重要的双重作用，包括化疗，放疗，抗血管生成和激素疗法以及免疫检查点阻断（ICB）免疫疗法。一些选定的化疗药物（如阿霉素）诱导肿瘤抗原和辅助分子的释放，巨噬细胞参与癌症免疫循环，这一过程称为免疫原性细胞死亡。细胞减灭疗法通过消耗巨噬细胞来靶向。曲维菌素是从海洋生物中提取的化合物，并被批准为治疗软组织肉瘤和卵巢癌的单一药物。曲维菌素及其类似物吕比西丁，最近被批准用于治疗NSCLC，通过肿瘤坏死因子受体超家族成员10（TNFRSF10，也称为TRAIL）的依赖性细胞凋亡途径选择性地消耗患者和小鼠的单核细胞以及TAM。TAM衰竭对于曲维菌素的抗肿瘤活性至关重要。选定的抗癌药物可以恢复TAM极化，增加5-氟尿嘧啶在结直肠癌中以及铂类辅助化疗在高等级卵巢癌中的应用。对于通过产生活性氧（ROS）诱导DNA损伤的药物，例如铂基化疗，肠道微生物组可以启动肿瘤内单核吞噬细胞以产生ROS，从而积极调节这些药物的疗效。在放射治疗的情况下，真菌的消耗增强了乳腺癌和黑色素瘤小鼠模型的辐射反应。图2：真菌生态失调增强肿瘤对辐射的反应03ICB免疫治疗释放T细胞介导的1型免疫反应是ICB免疫治疗的基石。骨髓单核细胞是免疫抑制通路的主要调节因子，是ICB反应的重要决定因素，并且对耐药性和这种治疗的资格至关重要。骨髓单核细胞是肿瘤外源性途径的一部分，ICB的原发性和适应性抵抗力通过表达几种免疫抑制分子来实现，包括检查点配体，如PDL1，PDL2，CD80（也称为B7-1）和CD86（也称为B7-2）和脊髓灰质炎病毒受体（PVR，也称为CD155和TIGIT配体之一）。通过免疫组化进行的PDL1评估被批准为NSCLC和其他肿瘤中抗PD1治疗的伴随诊断，但其预测能力可能因细胞类型而异。出乎意料的是，巨噬细胞表达PD1，与它们对肿瘤细胞的吞噬活性呈负相关。骨髓单核细胞表达其他受体，这些受体与T细胞和NK细胞表达的负调节因子相互作用。VISTA作为T细胞检查点抑制配体，由巨噬细胞表达并与P-选择蛋白糖蛋白配体1（PSGL1）相互作用。在人单核细胞中，针对VISTA的单克隆抗体引起转录和功能变化，包括抗原呈递、激活和迁移增加。巨噬细胞的消耗可以加强各种免疫治疗策略，包括疫苗接种和检查点抑制剂。结合检查点抑制剂和抗CSF1R抗体或其他以TAM为中心的治疗策略的几项临床试验正在进行中。表1：靶向肿瘤相关巨噬细胞的药物的部分临床试验04TAM 的功能重编程可以使用不同的策略实现 TAM 的功能重编程。图3：巨噬细胞重编程和激活先天性和适应性免疫反应1.TAM 募集和积累趋化因子和CSF1在肿瘤中单核细胞的募集和塑造它们在TME中的功能方面起着重要作用。单核细胞引诱剂，如CCL2及其同源受体CCR2，在实体瘤和血液系统恶性肿瘤中使用mAb和受体拮抗剂作为靶向。然而，尽管临床前模型有大量数据，但趋化因子靶向策略尚未单独或联合产生阳性临床结果，并且已经停止使用。临床前模型中的几项研究表明，CSF1R抑制降低了TAM的密度和肿瘤生长，并增加了对化疗的敏感性。虽然小分子抑制剂BLZ945没有耗尽TAM，但这些TAM经过了针对抗肿瘤表型的重编程。在CSF1R阻断后，巨噬细胞显示出促肿瘤基因的表达较低，并且与抗原呈递和淋巴细胞活化相关的基因上调。BLZ945重塑了免疫微环境，在TAM、产生IFNγ的NK和T细胞以及产生IL-12的树突状细胞之间诱导了正串扰，从而维持了抗肿瘤反应的良性网络。在罕见肿瘤（弥漫型腱鞘巨细胞）过度表达CSF1的患者中抑制CSF1R让71%的患者具有显著的临床获益。在其他实体瘤中，CSF1R抑制剂作为单一药物表现出色。一些临床试验已经评估了CSF1R抑制与化疗，放疗或ICB的组合。但大多数针对CSF1R的研究仍在进行中。因此，仍没有完全评估这种方法的临床益处。在不良反应方面，相当比例的治疗患者有脑眶周水肿。由于细胞外基质重塑，基质金属蛋白酶的活化和透明质酸沉积，导致液体潴留增加。2.补体补体已成为小鼠和人类癌症中促进炎症的重要组成部分。补体系统由由三种不同途径激活的蛋白水解反应级联组成：经典途径，其由C1q与免疫复合物的结合引发;凝集素途径，由甘露糖结合凝集素或纤维蛋白与受损细胞上病原体相关分子模式或异常碳水化合物结构的相互作用引发;替代途径，其直接被受损细胞或微生物激活。中枢组分C3和C5的活化导致其生物活性片段（过敏酶）的释放和细胞溶解膜攻击复合物的组装。非常规补体活化也可能由于凝血酶和纤维蛋白溶解酶的蛋白水解活性而发生。补体分子的预后潜力，特别是C4d，C5a和C5aR1，已经在不同类型的癌症中得到证实。例如，补体激活片段C4d在肺癌中用作诊断和预后标志物，在乳腺癌中用C5-C5aR1。而 C1 和 C4d 是RCC 患者预后不良的生物标志物。此外，癌症基因组图谱（TCGA）数据库中的转录组学数据显示，经典和替代途径基因的高表达与特定肿瘤的预后不良相关，包括黑色素瘤、神经胶质瘤、肺鳞癌和RCC。在RCC中，产生C1q的TAM的浸润与免疫抑制的TME相关，其特征在于免疫检查点分子（PD1，LAG3，PDL1和PDL2）的高表达，这表明补体活化与T细胞衰竭之间存在相关性。与这些数据一致，可溶性模式识别分子pentraxin 3（PTX3）可以通过调节肉瘤中补体依赖性和巨噬细胞持续的促进炎症来充当外在肿瘤抑制基因。3.炎性小体和IL-1虽然IL-1可以触发保护性免疫反应，但该途径的主要功能是促进癌变和转移。IL-1通过复杂的机制促进癌症相关的免疫抑制，包括MDSC的产生和招募，以及促进TAM免疫抑制。因此，在RCC模型中，与抗IL-1和抗PD1或多靶点酪氨酸激酶抑制剂卡维氮替尼的联合治疗导致协同抗肿瘤作用。IL-1可以直接靶向，通过卡那单抗，或通过炎症小体来抑制。例如，在小鼠黑色素瘤模型中，抑制肿瘤衍生的NLRP3（炎小体的传感器组分），有限的MDSC介导的T细胞抑制。NLRP3抑制的抗肿瘤电位通过联合抗PD1治疗进一步放大。这些结果需要使用抗IL-1和炎性粒体抑制剂进行实验。已经计划在发生肺癌高风险的患者（如重度吸烟者）中使用canakinumab（抗IL-1）进行药物预防试验。05巨噬细胞治疗TAM池通过招募循环单核细胞不断补充。CAR T细胞可有效治疗血液系统恶性肿瘤，但进入实体瘤是T细胞治疗的绊脚石。基于巨噬细胞的细胞疗法可以克服这一限制，因为单核吞噬细胞不断被运送到肿瘤中。基于巨噬细胞的细胞治疗策略要么将细胞因子或纳米颗粒传递给TME，要么基于用工程受体武装单核吞噬细胞。在一项概念验证研究中，补充了载药纳米颗粒的单核细胞静脉注射到肿瘤小鼠体内，能够以比游离纳米颗粒更高的效率到达肿瘤部位。De Palma等人研究了使用巨噬细胞将IFN-α带到肿瘤部位并因此激活免疫反应的可能性。在Tie2启动子下在造血祖细胞中转导Ifna1基因。表达Tie2的单核细胞具有高度肿瘤归巢能力，成功迁移到肿瘤并在TME中递送IFN-α，触发免疫细胞的活化并抑制肿瘤生长和血管生成。在小鼠肉瘤模型中，预转移性生态位的特征在于以骨髓细胞为中心的免疫抑制基因特征。骨髓细胞被基因工程改造以表达IL-12。在过继转移时，表达骨髓来源的骨髓细胞的IL-12在肺部引起1型免疫反应，并减少转移和原发性肿瘤生长。转导人巨噬细胞一直是开发基于单核吞噬细胞的细胞疗法的障碍，也是不同技术平台开发的绊脚石。CAR-M 携带识别癌胚抗原相关细胞粘附分子 5 （CEACAM5）、CD19、CD22、HER2 和 CD5 的受体已被开发用于治疗各种实体瘤。CAR-M细胞介导吞噬作用并以稳定的方式表达M1功能。目前正在进行或计划进行临床试验，以评估CAR-M在不同肿瘤中的潜力。图4：基于CAR-M细胞的细胞疗法06前景巨噬细胞在从化疗到ICB免疫治疗的治疗方式有效性中起着双重作用。在许多人类肿瘤中，TAM是T细胞检查点阻断的主要驱动因素，并介导对免疫治疗的耐药性。尽管直接靶向骨髓单核细胞在癌症的起源、进展和治疗中起着至关重要的作用，但迄今为止，它们未能产生重大的治疗效果，尽管正在进行的针对TAMs与其他治疗方式联合使用的试验可能会改变整体情况。TAM免疫学治疗中的绊脚石包括肿瘤中单核吞噬细胞的多样性和可塑性。单细胞水平上 TAM 多样性及其本体遗传关系可能为选择性地消耗肿瘤促进亚群与抑制肿瘤亚群的策略提供新的思路。空间和单细胞分析将需要在临床环境中进行评估以及治疗测试。参考文献：1.Shiao SL, Kershaw KM, Limon JJ, et al. Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy. Cancer Cell. 2021;39(9):1202-1213.e6. doi:10.1016/j.ccell.2021.07.0022.Mantovani A, Allavena P, Marchesi F, Garlanda C. Macrophages as tools and targets in cancer therapy [published online ahead of print, 2022 Aug 16]. Nat Rev Drug Discov. 2022;1-22. doi:10.1038/s41573-022-00520-5扫码加入BiG生物创新社读者交流群，分享、交流纯粹的行业知识，非诚勿扰！BiGScientific Driven, Making Impact!创新生态丨医药论坛丨行业分析媒体公关丨BiG Webinar联系我们商务：Max 18662346610媒体：Kathy 17621909690

免疫疗法放射疗法细胞疗法抗体疫苗

2022-10-31

·佰傲谷BioValley

不出意料丨FDA专家委员会16人一致反对Y-Mabs的B7H3 RDC上市

10月28日，Y-Mabs宣布FDA ODAC会议以16比0的结果一致反对该公司的B7H3特异性抗体131I-omburtamab（放射性核素偶联）用于治疗神经母细胞瘤（NB）的CNS/软脑膜转移。尽管此前该药物获得了上市优先审评资格，但因为其两项关键临床03-133和101中出现的许多严重问题，这一16比0的一致性结果并没有出乎大多数人的预料。扩展阅读：恐难通过丨FDA专家会对B7H3单抗omburtamab的三个担忧当然，临床上的严重问题也为B7H3这个靶点是否对于神经母细胞瘤来说可行带来了一个问号，不过目前其他癌种作为适应症也并不在少数。B7H3靶点以及其他同类型竞品B7-H3 (CD276)是一种I型跨膜糖蛋白分子，位于人15号染色体上，属于B7共刺激分子家族成员之一，在正常人组织中广泛转录，但其蛋白表达受到转录后控制的严格限制。多项研究表明，B7-H3存在于一系列脑癌中。不同类型的神经胶质瘤具有不同的B7-H3表达水平，而在正常组织中表达有限。B7H3这一靶点在目前ADC，CAR-T，抗体均对这一靶点有所布局。目前B7H3-CAR-T主要处于临床早期阶段，目前我国已披露的公司有博生吉的TAA-06，南京卡提的KT-032等等。除此之外还有大量IIT临床蓄势待发。（下图为部分临床）此前在Nature Communications上就披露过一个SynNotch门控 GD2/B7H3 CAR-T的临床前结果，该疗法将GD2识别为门，将B7H3识别为目标，通过门控策略减少毒性相关副作用。而在ADC方面，如第一三共已经披露了初步结果，在2022年ESMO上披露的小样本量DS-7300临床结果表明，在小细胞肺癌这一难治性癌症上，9位参与研究的患者有6人已被确认为部分缓解，还有一位部分缓解待确认，疾病控制率达到了77.8%，可以期待后续更多数据。小编总结目前NB的免疫治疗靶点在于GD2，B7H3，ALK上。从Y-Mabs公司已经上市的针对复发/难治性神经母细胞瘤GD2抗体DANYELZA来看，Y-Mabs公司可能有些死磕儿科和脑癌方面的癌种了，或许在其他癌种适应症方面也不会太差。参考来源：Aggarwal C, Prawira A, Antonia S, et al. Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial. J Immunother Cancer. 2022 Apr;10(4):e004424. doi: 10.1136/jitc-2021-004424.https://oncologypro.esmo.org/meeting-resources/esmo-congress/ds-7300-b7-h3-dxd-antibody-drug-conjugate-adc-shows-durable-antitumor-activity-in-advanced-solid-tumors-extended-follow-up-of-a-phase-i-ii-studyPark JA, Cheung NV. Targets and Antibody Formats for Immunotherapy of Neuroblastoma. J Clin Oncol. 2020 Jun 1;38(16):1836-1848. doi: 10.1200/JCO.19.01410. Epub 2020 Mar 13. PMID: 32167865; PMCID: PMC7255979.近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

抗体免疫疗法抗体药物偶联物优先审批细胞疗法