Programmable Off-the-Shelf Dendritic Cells as an Immunotherapy Discovery Platform
可编程现成树突状细胞作为免疫治疗发现平台
基本信息
- 批准号:10449196
- 负责人:
- 金额:$ 39.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdoptive ImmunotherapyAllelesAllogenicAntigen-Presenting CellsAntigensAutologousAwardBase PairingBasic ScienceBindingCell LineCell physiologyCellsClinicCommunicable DiseasesComplexConsumptionCustomCytotoxic T-LymphocytesDNADendritic Cell VaccineDendritic CellsEndogenous RetrovirusesEngineeringGenesGeneticGenomeGoalsHLA AntigensHaplotypesHarvestHumanHuman GenomeImmuneImmune systemImmunotherapyIn VitroIndustrializationInvestmentsLibrariesMalignant NeoplasmsMarshalMature T-LymphocyteMethodsModificationNational Institute of Allergy and Infectious DiseasePatientsPeptidesPersonsPopulationPositioning AttributeProceduresProliferatingReporterResearchResearch PersonnelRoleSafetySolid NeoplasmSourceStressStretchingSurfaceSystemT-Cell ActivationT-Cell ReceptorT-LymphocyteTechnologyTestingTherapeuticTimeTrainingTransgenesTumor AntigensTumor-Infiltrating LymphocytesUntranslated RNAVaccinesValidationVisionWorkWritingcancer immunotherapycareerchemotherapychimeric antigen receptorcombinatorialdirected differentiationefficacy testingengineered T cellsepigenetic silencinggenome-widehigh rewardhigh riskinduced pluripotent stem cellinduced pluripotent stem cell technologyinnovationinvestigator trainingmonocyteneoplastic cellnew technologynext generation sequencingnovel therapeuticsperipheral bloodprogramsreceptorrefractory cancersynthetic biologytechnology developmenttumor
项目摘要
Project Summary
Adoptive Cell Immunotherapy using patient harvested T cells engineered against tumor-specific targets has
ushered in a new therapeutic era. However, the lack of tumor-specific targets and T cell receptors limits the
addressable cancers. A promising approach for solid tumors uses T cell receptors (TCRs) directed against tumor-
specific antigens (TSAs) displayed on HLA receptors found on the surface of nearly every cell. Unfortunately,
HLAs are highly polymorphic genes between people. This restricts both the TCRs and TSAs to a small number
of patients. A platform that expands the number of HLA-restricted TSAs and TCRs will transform the entire
immunotherapy pipeline.
Here, I propose to address this unmet need by generating programmable Dendritic cells (DCs) – professional
antigen presenting cells that function to mature and activate naive T cells. Programmable DCs would permit the
discovery of new TCRs, validation of TSAs, and perhaps be used as "living" vaccines to marshal a patient’s own
immune system against infectious disease and cancer. Thus far, efforts to leverage the potential of DCs have
been limited principally by: (1) an inability to produce cells with HLAs matched to patients;; (2) an inability to
robustly test and validate new TSAs against TCRs;; and (3) an inability to produce "off-the-shelf" DCs at industrial
scale.
As a new innovator, my vision is to produce off-the-shelf Dendritic Cells pre-engineered to match any HLA
haplotype (even rare ones) and pre-encoded with any combination of TSAs. Using this new platform, my group
will search for and validate "universal" TSAs/TCRs that can be used broadly in TCR-Therapy for any patient.
Specifically, we will focus on peptides expressed from regions of the genome normally epigenetically silenced,
but re-activated in tumor cells (such as endogenous retroviruses). To reach this goal, we will continue
development of technology enabling the "writing" of millions of base-pairs of DNA in human induced pluripotent
stem cells (iPSCs). This technology allows direct customization of the large HLA locus of iPSCs in a single step;;
introduction of libraries of potential TSAs;; and integration of synthetic reporter constructs (which are excisable
for safety) for enhancing the in vitro directed differentiation of iPSCs to DCs. Thus, allogeneic programmed DCs
will catalyze a wide variety of immunotherapy applications and expand access of these advanced treatments for
a greater number of patients.
项目总结
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
David Minh Truong其他文献
David Minh Truong的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('David Minh Truong', 18)}}的其他基金
Programmable Off-the-Shelf Dendritic Cells as an Off-the-Shelf Immunotherapy Discovery Platform
可编程现成树突状细胞作为现成免疫治疗发现平台
- 批准号:
10564837 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Programmable Off-the-Shelf Dendritic Cells as an Immunotherapy Discovery Platform
可编程现成树突状细胞作为免疫治疗发现平台
- 批准号:
10684656 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Programmable Off-the-Shelf Dendritic Cells as an Immunotherapy Discovery Platform
可编程现成树突状细胞作为免疫治疗发现平台
- 批准号:
10051095 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Programmable Off-the-Shelf Dendritic Cells as an Immunotherapy Discovery Platform
可编程现成树突状细胞作为免疫治疗发现平台
- 批准号:
10770601 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Humanized synthetic chromosomes built in yeast for organ xenotransplantation
酵母中内置人源化合成染色体用于器官异种移植
- 批准号:
9305101 - 财政年份:2015
- 资助金额:
$ 39.17万 - 项目类别:
Humanized synthetic chromosomes built in yeast for organ xenotransplantation
酵母中内置人源化合成染色体用于器官异种移植
- 批准号:
8982620 - 财政年份:2015
- 资助金额:
$ 39.17万 - 项目类别:
Humanized synthetic chromosomes built in yeast for organ xenotransplantation
酵母中内置人源化合成染色体用于器官异种移植
- 批准号:
9115472 - 财政年份:2015
- 资助金额:
$ 39.17万 - 项目类别:
相似海外基金
VLA-4–targeted 67Cu-LLP2A preconditioning enhances efficacy of T-cell-based adoptive immunotherapy
VLA-4™ 靶向 67Cu-LLP2A 预处理增强基于 T 细胞的过继免疫疗法的疗效
- 批准号:
10713034 - 财政年份:2023
- 资助金额:
$ 39.17万 - 项目类别:
Phase I first-in-human trial for ThINKK adoptive immunotherapy in children with high-risk cancers
针对高危癌症儿童的ThINKK过继免疫疗法的I期首次人体试验
- 批准号:
484371 - 财政年份:2023
- 资助金额:
$ 39.17万 - 项目类别:
Operating Grants
Phase I first-in-human trial of ThINKK adoptive immunotherapy in children with high-risk cancers
针对高危癌症儿童的ThINKK过继免疫疗法的I期首次人体试验
- 批准号:
473376 - 财政年份:2022
- 资助金额:
$ 39.17万 - 项目类别:
Operating Grants
Development of Adoptive Immunotherapy Focusing on Follicular Helper T Cell Biology
专注于滤泡辅助 T 细胞生物学的过继免疫疗法的发展
- 批准号:
21K16420 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10180117 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10364687 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer
数学模型引导的膀胱癌过继免疫治疗
- 批准号:
10599851 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Development of a combinatorial approach of antibody therapeutics and adoptive immunotherapy for cancer
开发抗体疗法和癌症过继免疫疗法的组合方法
- 批准号:
21K19422 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Elucidation of the function of the new NK cell subset and its application to adoptive immunotherapy
阐明新NK细胞亚群的功能及其在过继性免疫治疗中的应用
- 批准号:
21H04832 - 财政年份:2021
- 资助金额:
$ 39.17万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Adoptive immunotherapy for adult T-cell leukemia/lymphoma with ex vivo expanded multi-tumor associated antigen specific cytotoxic T-cells
使用离体扩增的多肿瘤相关抗原特异性细胞毒性 T 细胞对成人 T 细胞白血病/淋巴瘤进行过继免疫治疗
- 批准号:
20K17375 - 财政年份:2020
- 资助金额:
$ 39.17万 - 项目类别:
Grant-in-Aid for Early-Career Scientists