Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)
用于指导序贯靶向抑制剂的时空肿瘤分析:免疫治疗组合(ST-Analytics)
基本信息
- 批准号:10526101
- 负责人:
- 金额:$ 270.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-22 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdoptive Cell TransfersAlgorithmsAutomobile DrivingBiologicalBiopsyCell physiologyCellsClinicalClinical DataClinical TrialsClinical Trials DesignCombination immunotherapyCombined Modality TherapyCommunitiesCoupledDataDatabasesDevelopmentDisadvantagedDisease modelDistalDoseEducation and OutreachEducational ModelsEnvironmentEnvironment DesignEpigenetic ProcessEvaluationGenetic TranscriptionImmuneImmune systemImmunologic FactorsImmunooncologyImmunotherapyIndividualInternshipsK-12 EducationKineticsKnowledgeLeadLeadershipMalignant NeoplasmsMeasurementMetastatic malignant neoplasm to brainMitogen-Activated Protein Kinase InhibitorModelingNatureNeoplasm MetastasisOutcomePatientsPharmaceutical PreparationsPilot ProjectsPlayPrimary NeoplasmProteomicsResearchResearch PersonnelResearch Project GrantsResistanceResourcesRoleScienceScience, Technology, Engineering and Mathematics EducationScientistSelf-ExaminationSeriesStructureSystemSystems BiologyTherapeuticTimeTissuesVisualWorkbasebiobankcancer immunotherapycombinatorialcomputing resourcesdemographicsdesignimmune checkpoint blockadein silicoin vivoinhibitorinhibitor therapymedical schoolsmelanomamodel designmouse modelmultiple omicsoutreachoutreach programpreventprogramsrecruitspatiotemporaltooltranscriptomicstumortumor-immune system interactions
项目摘要
Overall Project Summary
The proposed U54 program Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor --
Immunotherapy Combinations (ST-Analytics) is designed to develop the recent conceptual advance that
targeted inhibitor + cancer immunotherapy (IT) combination treatments may yield significantly greater patient
benefit if those treatments are administered in sequence rather than simultaneously. Analysis of retrospective
clinical data coupled with in vivo therapeutic modeling using syngeneic models of murine melanoma strongly
support this concept. In fact, the picture that has emerged in melanoma is that immune factors can play a strong
role in driving resistance to MAPK inhibitor (MAPKi) therapy, and that lead-in immune checkpoint blockade (ICB)
can ‘prime’ both the primary tumor and distal metastases (including brain metastases) for eradication when the
IT is subsequently combined with MAPKi. This observation opens the doors for immune based strategies, such
as ICB or adoptive cell therapy (ACT), as sequential combinatorial agents to prevent MAPKi resistance.
However, this concept introduces a number of new variables, including dosing, sequence, and timing. This can
make the design and execution of clinical trials that can yield statistically significant outcomes impractical. This
is the scientific and translational problem we address in the proposed ST-Analytics U54.
The ST-Analytics U54 center is populated by leading scientists at the ISB, the UCLA Geffen School of Medicine,
and Yale, and is comprised of two research projects and two research cores, with each project integrating both
state-of-the-art experimentation and computational work. This structure is further designed to bring together the
scientific, experimental, and computational and administrative resources to develop a data base that captures
the kinetics of lead-in monotherapy tumor priming, and apply that data base to the development of predictive in
silico models that can inform the design of such targeted inhibitor – immunotherapy sequence combinations for
clinical trials. This requires close integration and cycles of iteration between of state-of-the-art experimentation,
leading edge computation, and realistic disease models, continuously calibrated through the analysis of highly
relevant, biopsied patient tumors. The resulting science also provides exciting opportunities for high impact
STEM outreach. We propose to act on those opportunities by leveraging a long-standing systems education
outreach program at ISB that already has impacted K-12 STEM education in all 50 states, and places an
emphasis on those communities that have been historically under-represented in STEM.
整体项目总结
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)
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James R. Heath其他文献
Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- DOI:
10.1186/s13073-023-01278-0 - 发表时间:
2024-01-06 - 期刊:
- 影响因子:11.200
- 作者:
Daniela Matuozzo;Estelle Talouarn;Astrid Marchal;Peng Zhang;Jeremy Manry;Yoann Seeleuthner;Yu Zhang;Alexandre Bolze;Matthieu Chaldebas;Baptiste Milisavljevic;Adrian Gervais;Paul Bastard;Takaki Asano;Lucy Bizien;Federica Barzaghi;Hassan Abolhassani;Ahmad Abou Tayoun;Alessandro Aiuti;Ilad Alavi Darazam;Luis M. Allende;Rebeca Alonso-Arias;Andrés Augusto Arias;Gokhan Aytekin;Peter Bergman;Simone Bondesan;Yenan T. Bryceson;Ingrid G. Bustos;Oscar Cabrera-Marante;Sheila Carcel;Paola Carrera;Giorgio Casari;Khalil Chaïbi;Roger Colobran;Antonio Condino-Neto;Laura E. Covill;Ottavia M. Delmonte;Loubna El Zein;Carlos Flores;Peter K. Gregersen;Marta Gut;Filomeen Haerynck;Rabih Halwani;Selda Hancerli;Lennart Hammarström;Nevin Hatipoğlu;Adem Karbuz;Sevgi Keles;Christèle Kyheng;Rafael Leon-Lopez;Jose Luis Franco;Davood Mansouri;Javier Martinez-Picado;Ozge Metin Akcan;Isabelle Migeotte;Pierre-Emmanuel Morange;Guillaume Morelle;Andrea Martin-Nalda;Giuseppe Novelli;Antonio Novelli;Tayfun Ozcelik;Figen Palabiyik;Qiang Pan-Hammarström;Rebeca Pérez de Diego;Laura Planas-Serra;Daniel E. Pleguezuelo;Carolina Prando;Aurora Pujol;Luis Felipe Reyes;Jacques G. Rivière;Carlos Rodriguez-Gallego;Julian Rojas;Patrizia Rovere-Querini;Agatha Schlüter;Mohammad Shahrooei;Ali Sobh;Pere Soler-Palacin;Yacine Tandjaoui-Lambiotte;Imran Tipu;Cristina Tresoldi;Jesus Troya;Diederik van de Beek;Mayana Zatz;Pawel Zawadzki;Saleh Zaid Al-Muhsen;Mohammed Faraj Alosaimi;Fahad M. Alsohime;Hagit Baris-Feldman;Manish J. Butte;Stefan N. Constantinescu;Megan A. Cooper;Clifton L. Dalgard;Jacques Fellay;James R. Heath;Yu-Lung Lau;Richard P. Lifton;Tom Maniatis;Trine H. Mogensen;Horst von Bernuth;Alban Lermine;Michel Vidaud;Anne Boland;Jean-François Deleuze;Robert Nussbaum;Amanda Kahn-Kirby;France Mentre;Sarah Tubiana;Guy Gorochov;Florence Tubach;Pierre Hausfater;Isabelle Meyts;Shen-Ying Zhang;Anne Puel;Luigi D. Notarangelo;Stephanie Boisson-Dupuis;Helen C. Su;Bertrand Boisson;Emmanuelle Jouanguy;Jean-Laurent Casanova;Qian Zhang;Laurent Abel;Aurélie Cobat - 通讯作者:
Aurélie Cobat
C60's smallest cousin
C60 的最小“亲戚”
- DOI:
10.1038/31579 - 发表时间:
1998-06-25 - 期刊:
- 影响因子:48.500
- 作者:
James R. Heath - 通讯作者:
James R. Heath
Protein Catalyzed Capture (PCC) Agents for Antigen Targeting.
用于抗原靶向的蛋白质催化捕获 (PCC) 试剂。
- DOI:
- 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
M. Idso;B. Lai;Heather D Agnew;James R. Heath - 通讯作者:
James R. Heath
Planar Patch-Clamp Electrodes for Single Cell and Neural Network Studies
- DOI:
10.1016/j.bpj.2009.12.3287 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
John M. Nagarah;Daniel A. Wagenaar;James R. Heath - 通讯作者:
James R. Heath
Stereochemical engineering of a peptide macrocycle allosteric inhibitor of phospho-Akt2 controls cell penetration by fine-tuning macrocycle-cell membrane interactions
磷酸 Akt2 肽大环变构抑制剂的立体化学工程通过微调大环 - 细胞膜相互作用来控制细胞渗透
- DOI:
10.26434/chemrxiv-2021-kldh7 - 发表时间:
2021 - 期刊:
- 影响因子:5.9
- 作者:
Arundhati Nag;A. Mafi;Samir R Das;Mary Beth Yu;Belen Alvarez;W. Goddard;James R. Heath - 通讯作者:
James R. Heath
James R. Heath的其他文献
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{{ truncateString('James R. Heath', 18)}}的其他基金
Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)
用于指导序贯靶向抑制剂的时空肿瘤分析:免疫治疗组合(ST-Analytics)
- 批准号:
10708901 - 财政年份:2022
- 资助金额:
$ 270.26万 - 项目类别:
PROJECT 1: TIME-Based Spatiotemporal Cancer Immunograms Predictive for Immunotherapy-Targeted Therapy Sequential Combinations
项目 1:基于时间的时空癌症免疫图预测免疫治疗靶向治疗顺序组合
- 批准号:
10907268 - 财政年份:2022
- 资助金额:
$ 270.26万 - 项目类别:
PROJECT 1: TIME-Based Spatiotemporal Cancer Immunograms Predictive for Immunotherapy-Targeted Therapy Sequential Combinations
项目 1:基于时间的时空癌症免疫图预测免疫治疗靶向治疗顺序组合
- 批准号:
10526103 - 财政年份:2022
- 资助金额:
$ 270.26万 - 项目类别:
PROJECT 1: TIME-Based Spatiotemporal Cancer Immunograms Predictive for Immunotherapy-Targeted Therapy Sequential Combinations
项目 1:基于时间的时空癌症免疫图预测免疫治疗靶向治疗顺序组合
- 批准号:
10708924 - 财政年份:2022
- 资助金额:
$ 270.26万 - 项目类别:
Data-driven Patient-Specific Agent Based Models of Metastatic Melanoma for Immunotherapy Response Prediction
用于免疫治疗反应预测的数据驱动的基于患者特异性药物的转移性黑色素瘤模型
- 批准号:
10831325 - 财政年份:2022
- 资助金额:
$ 270.26万 - 项目类别:
Nano and biomolecular engineered technologies for neoantigen-specific T cell capture and characterization
用于新抗原特异性 T 细胞捕获和表征的纳米和生物分子工程技术
- 批准号:
10297588 - 财政年份:2021
- 资助金额:
$ 270.26万 - 项目类别:
Nano and biomolecular engineered technologies for neoantigen-specific T cell capture and characterization
用于新抗原特异性 T 细胞捕获和表征的纳米和生物分子工程技术
- 批准号:
10489832 - 财政年份:2021
- 资助金额:
$ 270.26万 - 项目类别:
Nano and biomolecular engineered technologies for neoantigen-specific T cell capture and characterization
用于新抗原特异性 T 细胞捕获和表征的纳米和生物分子工程技术
- 批准号:
10673935 - 财政年份:2021
- 资助金额:
$ 270.26万 - 项目类别: