Enhancing Chimeric Antigen Receptor T Cell Therapies for Hematologic Malignancies: Beyond CART 19
增强嵌合抗原受体 T 细胞治疗血液恶性肿瘤:超越 CART 19
基本信息
- 批准号:9280418
- 负责人:
- 金额:$ 289.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-15 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:Acute Lymphocytic LeukemiaAcute Myelocytic LeukemiaAcute T Cell LeukemiaAcute leukemiaAddressAdoptive TransferB lymphoid malignancyB-LymphocytesBackBiologicalBiometryCD19 geneCD22 geneCRISPR/Cas technologyCell TherapyCellsChronic Lymphocytic LeukemiaClinicClinicalClinical TrialsCollaborationsDataDevelopmentDisciplineDiseaseEmployee StrikesGeneticGenetic EngineeringGoalsHematologic NeoplasmsHematopoiesisHematopoietic NeoplasmsImmunologicsImmunotherapyIn complete remissionInternationalJournalsLaboratoriesLymphoblastic LeukemiaMalignant NeoplasmsMarrowMediatingMedicalMedicineMonitorMultiple MyelomaMyeloid LeukemiaNew EnglandPaperPatientsPopulationPublishingRNARefractoryRelapseResearchResearch PersonnelResistanceResource SharingRoleSafetySamplingSurface AntigensT-LymphocyteTechnologyTestingTherapeuticTranslatingUnited StatesVariantantitumor effectauthoritybench to bedsidecancer immunotherapychimeric antigen receptorclinical investigationhigh dimensionalityimmune checkpointimprovedinnovationkillingsleukemiamanufacturing facilityneoplasticnext generationnovel therapeuticspreclinical studyprogramssuccesssynthetic biologytherapy resistant
项目摘要
OVERALL SUMMARY
The long-term goal of this P01 is to develop next generation immunotherapy with chimeric antigen receptor
(CAR) T cells and to translate this research into new therapies with curative potential for patients with blood
cancer. The CAR developed at our center is now in international trials for refractory/relapsed pre-B cell acute
lymphocytic leukemia (ALL). However, multiple myeloma (MM), acute myeloid leukemia (AML) and chronic
lymphocytic leukemia (CLL) remain as the major unmet medical need in blood cancers. Our central hypothesis
is that therapies with combination of CAR T cells and universal CAR T cells created with CRISPR/Cas9 genetic
editing will enable this powerful therapy to reach a broader spectrum of patients with blood cancer. We have
brought together a cadre of exceptional investigators from multiple disciplines who have collaborated and
published together for many years. Each disease-focused project will be led by a recognized authority in the
field. To achieve our goals, we have developed three Projects, which will coordinately closely with essential
shared resource cores. In Project 1, we will determine the clinical and immunological impact of treating patients
on two clinical trials: (i) CAR T cells targeting CD19 and CD22 will be used to address the remaining unmet
medical need in ALL, which is the emergence of CD19 escape variants; and (ii) universal CAR T cells targeting
CD19 will be tested in patients with CLL to determine the role of T cell intrinsic resistance to therapy. In AML,
the central problem in CAR T cell therapy is the lack of a known surface antigen that is present on AML but
lacking from normal hematopoiesis. The goal of Project 2 is to open a wide therapeutic window by genetically
modifying normal marrow to make it resistant to killing by anti-AML CAR T cells, and delivering potent anti-
leukemic CAR T cells specific for CD33. In Project 3, the overall hypothesis is that anti-myeloma efficacy will be
maximized by (i) combining CART-BCMA and CTL019 to eliminate both the dominant neoplastic PC population
and rare myeloma-propagating B cells, and (ii) modifying CAR T cells to circumvent specific myeloma-induced
T-cell-inhibitory mechanisms (i.e., immune checkpoints).
The Cores for this P01 are essential for our progress including provision of project management for collaboration
and biostatistics, clinical safety and monitoring, and fiscal support (Core A), a GMP facility for manufacture of
cells and RNA (Core B), and a state-of-the-art platform for GLP analysis to provide high dimensional data of the
samples generated in all Projects (Core C). The potential for paradigm shifting impact is to transform the lessons
of CAR T for ALL into meaningful efficacy against all hematologic malignancies.
整体总结
项目成果
期刊论文数量(0)
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CARL H. JUNE其他文献
CARL H. JUNE的其他文献
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{{ truncateString('CARL H. JUNE', 18)}}的其他基金
Directing the metabolic fate of CAR T cells
指导 CAR T 细胞的代谢命运
- 批准号:
10364746 - 财政年份:2018
- 资助金额:
$ 289.74万 - 项目类别:
Enhancing Chimeric Antigen Receptor T Cell Therapies for HematologicMalignancies: Beyond CART 19
增强嵌合抗原受体 T 细胞治疗血液恶性肿瘤:超越 CART 19
- 批准号:
10713199 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Project 2: Towards a safe and effective AML treatment strategy using anti-CD33 CAR T cells in combination with CAR-resistant hematopoietic stem cells
项目2:利用抗CD33 CAR T细胞联合CAR耐药造血干细胞,制定安全有效的AML治疗策略
- 批准号:
10245064 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Core A: Administrative and Biostatistics Core
核心 A:行政和生物统计学核心
- 批准号:
10245066 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Project 2: Towards a safe and effective AML treatment strategy using anti-CD33 CAR T cells in combination with CAR-resistant hematopoietic stem cells
项目2:利用抗CD33 CAR T细胞联合CAR耐药造血干细胞,制定安全有效的AML治疗策略
- 批准号:
9982244 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Enhancing Chimeric Antigen Receptor T Cell Therapies for Hematologic Malignancies: Beyond CART 19
增强嵌合抗原受体 T 细胞治疗血液恶性肿瘤:超越 CART 19
- 批准号:
10245062 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Enhancing Chimeric Antigen Receptor T Cell Therapies for Hematologic Malignancies: Beyond CART 19
增强嵌合抗原受体 T 细胞治疗血液恶性肿瘤:超越 CART 19
- 批准号:
9982239 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
Core A: Administrative and Biostatistics Core
核心 A:行政和生物统计学核心
- 批准号:
9982247 - 财政年份:2017
- 资助金额:
$ 289.74万 - 项目类别:
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- 资助金额:
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DETERMINANTS OF RESPONSE OF ACUTE MYELOCYTIC LEUKEMIA
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