Phase I study of B7-H3 targeting CAR-T cells administered by local delivery in paediatric high risk brain tumour patients.
B7-H3 靶向 CAR-T 细胞的 I 期研究通过局部递送在儿科高危脑肿瘤患者中进行。
基本信息
- 批准号:MR/X030199/1
- 负责人:
- 金额:$ 485.21万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Childhood brain tumours that cannot be surgically removed or are insensitive to chemotherapy or radiotherapy represent a major clinical unmet need in paediatric oncology. There has been little improvement in outcome for these patients in recent decades despite numerous clinical trials of new treatments. In this research proposal we are seeking to evaluate a new approach to this high-risk patient group through a phase I clinical trial in which a new treatment (chimeric antigen receptor: CAR-T cells) and new route of administration (direct injection of cells into the region of the tumour) is evaluated in patients lacking other treatment options.The principle underlying CAR-T cell technology is that a blood sample is taken from the patient, and the killer cells of the immune system (T cells) are genetically modified in the lab, so as to specifically recognise cancer cells, but not normal cells. These genetically-modified therapeutic cells constitute a "cellular therapy", and we term them "killer T-cells". Following safety and quality testing, the gene-modified killer T-cells can be administered back to the patient, and the effect on tumour growth can be evaluated by serial tumour imaging, and by collection and analysis of patient samples. In the proposed clinical trial, particular innovation lies in three main areas. Firstly, the particular genetic modification to be trialled is new; ie a new DNA sequence encoding a new molecular structure on the surface of the killer T-cells. This novel structure incorporates a new recognition component for the cancer cells, and also incorporates a molecular switch allowing the activity of the killer T-cells to be switched on and off by use of a drug. Hence the trial needs first and foremost to test the safety of this approach. Secondly, we will evaluate if these gene-modified killer cells work without giving prior chemotherapy treatments to the patients. Chemotherapy pre-treatment has been previously considered essential for function of injected killer T cells. However, the chemotherapy also can increase overall toxicity for the patient, and can limit the number of treatments that can be safely given to an individual patient. Thirdly, we will use a novel mode of delivery, which is direct injection of the gene modified killer T-cells into the fluid that bathes the brain (cerebrospinal fluid). This will act as an alternate efficient delivery system and potentially will overcome the limitations of delivering killer T cells to brain tumours by the traditional approach of injection into the bloodstream. Each patient will receive up to three scheduled infusions, with further infusions allowed if there is clinical benefit. It is planned that a total of 18 patients will be recruited.
不能手术切除或对化疗或放疗不敏感的儿童脑肿瘤代表了儿科肿瘤学中未满足的主要临床需求。近几十年来,尽管有许多新疗法的临床试验,但这些患者的结局几乎没有改善。在这项研究提案中,我们正在寻求通过I期临床试验评估针对这一高危患者群体的新方法,(嵌合抗原受体:CAR-T细胞)和新的给药途径在缺乏其他治疗选择的患者中评估CAR-1(将细胞直接注射到肿瘤区域)的原理。T细胞技术是从患者身上提取血液样本,并在实验室中对免疫系统的杀伤细胞(T细胞)进行遗传修饰,以便特异性识别癌细胞,而不是正常细胞。这些基因修饰的治疗细胞构成了“细胞疗法”,我们称它们为“杀伤T细胞”。在安全性和质量测试之后,可以将基因修饰的杀伤T细胞施用于患者,并且可以通过连续肿瘤成像以及通过收集和分析患者样本来评估对肿瘤生长的影响。在拟议的临床试验中,特别的创新在于三个主要领域。首先,要试验的特定遗传修饰是新的;即在杀伤性T细胞表面编码新分子结构的新DNA序列。这种新的结构结合了一种新的癌细胞识别成分,还结合了一种分子开关,允许通过使用药物打开和关闭杀伤T细胞的活性。因此,试验首先需要测试这种方法的安全性。其次,我们将评估这些基因修饰的杀伤细胞是否在没有预先给予患者化疗的情况下起作用。化疗预处理以前被认为对注射的杀伤T细胞的功能至关重要。然而,化疗也可能增加患者的总体毒性,并可能限制可以安全地给予个体患者的治疗次数。第三,我们将使用一种新的输送模式,即直接将基因修饰的杀伤T细胞注射到大脑(脑脊液)中。这将作为一种替代的有效递送系统,并有可能克服通过传统的注射到血流中的方法将杀伤性T细胞递送到脑肿瘤的局限性。每名患者将接受最多三次预定输注,如果有临床获益,则允许进一步输注。计划共招募18名患者。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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William Anderson其他文献
TCT-824 The impact of creation of a transcatheter aortic valve program on surgical aortic valve replacement (sAVR) volume and outcomes: A single center experience
- DOI:
10.1016/j.jacc.2012.08.870 - 发表时间:
2012-10-23 - 期刊:
- 影响因子:
- 作者:
Firas Zahr;William Anderson;Thomas Gleason;Forozan Navid;Lisa Henry;Suresh Mulukutla;William Katz;Frederick Crock;Joon Lee;John Schindler - 通讯作者:
John Schindler
Impact of Electronic Medication Monitoring on Pediatric Asthma Severity and Control in a Real-World Multidisciplinary Clinic
- DOI:
10.1016/j.jaci.2021.12.755 - 发表时间:
2022-02-01 - 期刊:
- 影响因子:11.200
- 作者:
Matthew McCulloch;Samantha Bothwell;John Brinton;William Anderson - 通讯作者:
William Anderson
Neuroendocrine Mechanisms, Stress Coping Strategies, and Social Dominance: Comparative Lessons about Leadership Potential
神经内分泌机制、压力应对策略和社会支配地位:领导潜力的比较经验教训
- DOI:
- 发表时间:
2007 - 期刊:
- 影响因子:0
- 作者:
William Anderson;C. Summers - 通讯作者:
C. Summers
Career Readiness Identified as Unmet Need in Fellowship Training
职业准备在研究金培训中被确定为未满足的需求
- DOI:
10.1016/j.jaci.2021.12.694 - 发表时间:
2022-02-01 - 期刊:
- 影响因子:11.200
- 作者:
Maureen Bauer;William Anderson;Cullen Dutmer;Fred Atkins - 通讯作者:
Fred Atkins
189: Fetal tolerance of labor in pregnancies complicated by growth restriction and abnormal umbilical artery Doppler
- DOI:
10.1016/j.ajog.2016.11.093 - 发表时间:
2017-01-01 - 期刊:
- 影响因子:
- 作者:
Matthew M. Finneran;Drew Benac;Haley Stehr;William Anderson;Rebecca Pollack - 通讯作者:
Rebecca Pollack
William Anderson的其他文献
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{{ truncateString('William Anderson', 18)}}的其他基金
Asynchronous-coupled large-eddy simulation of Langmuir turbulence and the atmospheric surface layer
朗缪尔湍流和大气表层的异步耦合大涡模拟
- 批准号:
2054756 - 财政年份:2021
- 资助金额:
$ 485.21万 - 项目类别:
Standard Grant
NSF BSF: The Effect of Spanwise Landscape Heterogeneities on the Hydrological Cycle in the Atmospheric Boundary Layer
NSF BSF:跨度景观异质性对大气边界层水文循环的影响
- 批准号:
1839929 - 财政年份:2018
- 资助金额:
$ 485.21万 - 项目类别:
Standard Grant
Collaborative Research: Coordinated Experiments and Simulations of Near-Surface Turbulent Flow over Barchan Dunes: Informing Models of Dune Migration and Interaction
合作研究:新月形沙丘近地表湍流的协调实验和模拟:为沙丘迁移和相互作用模型提供信息
- 批准号:
1603254 - 财政年份:2016
- 资助金额:
$ 485.21万 - 项目类别:
Standard Grant
Dust Transport in Convectively Stratified Atmospheric Boundary Layer
对流分层大气边界层中的粉尘输送
- 批准号:
1500224 - 财政年份:2015
- 资助金额:
$ 485.21万 - 项目类别:
Continuing Grant
MRI R2: Acquisition of the next generation IRMS and CRDS for the SERC Stable Isotope Laboratory
MRI R2:为 SERC 稳定同位素实验室采购下一代 IRMS 和 CRDS
- 批准号:
0959722 - 财政年份:2010
- 资助金额:
$ 485.21万 - 项目类别:
Standard Grant
Workshop: Disasters Roundtable 2008
研讨会:2008 年灾害圆桌会议
- 批准号:
0809193 - 财政年份:2008
- 资助金额:
$ 485.21万 - 项目类别:
Standard Grant
COLLABORATIVE RESEARCH: Systematics and Evolution of Malpighiaceae
合作研究:金虎尾科的系统学和进化
- 批准号:
0543909 - 财政年份:2006
- 资助金额:
$ 485.21万 - 项目类别:
Continuing Grant
Disaster Research in the Social Sciences: Future Challenges and Opportunities
社会科学灾害研究:未来的挑战和机遇
- 批准号:
0342225 - 财政年份:2004
- 资助金额:
$ 485.21万 - 项目类别:
Continuing Grant
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