Summary of Study ST003963

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002483. The data can be accessed directly via it's Project DOI: 10.21228/M8PJ91 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003963
Study TitleImmunometabolic determinants of long-term response in preinfusion CAR-T cells of the leukemia patients receiving CD19 CAR T cell therapy
Study TypeUntargeted metabolomics
Study SummaryTo interrogate the immunometabolic properties of pre-infusion CAR-T cell products of both long-term and short-term responders, pre-infusion CAR-T cells were subjected untargeted metabolomics. We saw TCA metabolites, nucleotide biosynthesis intermediates, sphingolipid metabolism, and intermediates in central energy metabolism were significantly higher in long-term responders and nucleotide catabolic and tRNA metabolism intermediates were significantly decreased in long-term responders compared to short-term responders suggesting higher oxidative phosphorylation and fatty acid oxidation and pentose phosphate pathway contributing to higher antileukemic activity of CAR-T cells in long-term responders.
Institute
Translational Genomics Research Institute
Last NamePirrotte
First NamePatrick
Address445 N 5TH STREET, Phoenix, Arizona
Emailims@tgen.org
Phone16023438454
Submit Date2025-05-30
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-07-07
Release Version1
Patrick Pirrotte Patrick Pirrotte
https://dx.doi.org/10.21228/M8PJ91
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002483
Project DOI:doi: 10.21228/M8PJ91
Project Title:Metabolomics of CAR-T cells and their products in leukemia patients
Project Type:Untargeted metabolomics
Project Summary:Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. We applied an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) had increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR had high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induced metabolic reprogramming and enhanced anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission.
Institute:Translational Genomics Research Institute
Last Name:Pirrotte
First Name:Patrick
Address:445 N 5TH STREET, Phoenix, Arizona
Email:ims@tgen.org
Phone:6023438454
Funding Source:NIH K12 grant no. 5K12CA001727–29, The Hyundai Hope on Wheels Young Investigator Award, NCI grant no.P30CA033572
Project Comments:Study 1 of 4
Contributors:Lior Goldberg, Eric R. Haas, Jiaqi Wu, Bryan Garcia, Ryan Urak, Vibhuti Vyas, Ruby Espinosa, Tamara Munoz, Shirley Bierkatz, Jamie R. Wagner, Jinny Paul, Mary C. Clark, Dat Ngo, Ibrahim Aldoss, Stephen J. Forman & Xiuli Wang

Subject:

Subject ID:SU004100
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:33-52
Gender:Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Outcome
SA452839CARTG13xUPN518_RPnegCAR-T cells Long term responders
SA452840CARTG9xUPN552_HILICnegCAR-T cells Long term responders
SA452841CARTG9xUPN552_HILICposCAR-T cells Long term responders
SA452842CARTG10xUPN505_HILICposCAR-T cells Long term responders
SA452843CARTG10xUPN505_RPposCAR-T cells Long term responders
SA452844CARTG12xUPN544_RPnegCAR-T cells Long term responders
SA452845CARTG12xUPN544_RPposCAR-T cells Long term responders
SA452846CARTG13xUPN518_RPposCAR-T cells Long term responders
SA452847CARTG8xUPN495_HILICnegCAR-T cells Long term responders
SA452848CARTG1xUPN188_RPnegCAR-T cells Long term responders
SA452849CARTG1xUPN188_RPposCAR-T cells Long term responders
SA452850CARTG8xUPN495_RPnegCAR-T cells Long term responders
SA452851CARTG8xUPN495_RPposCAR-T cells Long term responders
SA452852CARTG9xUPN552_RPnegCAR-T cells Long term responders
SA452853CARTG9xUPN552_RPposCAR-T cells Long term responders
SA452854CARTG8xUPN495_HILICposCAR-T cells Long term responders
SA452855CARTG10xUPN505_HILICnegCAR-T cells Long term responders
SA452856CARTG10xUPN505_RPnegCAR-T cells Long term responders
SA452857CARTG13xUPN518_HILICnegCAR-T cells Long term responders
SA452858CARTG1xUPN188_HILICnegCAR-T cells Long term responders
SA452859CARTG1xUPN188_HILICposCAR-T cells Long term responders
SA452860CARTG13xUPN518_HILICposCAR-T cells Long term responders
SA452861CARTG12xUPN544_HILICposCAR-T cells Long term responders
SA452862CARTG12xUPN544_HILICnegCAR-T cells Long term responders
SA452863CARTG7xUPN466_RPposCAR-T cells Short term responders
SA452864CARTG7xUPN466_RPnegCAR-T cells Short term responders
SA452865CARTG6xUPN549_RPposCAR-T cells Short term responders
SA452866CARTG6xUPN549_RPnegCAR-T cells Short term responders
SA452867CARTG5xUPN431_RPnegCAR-T cells Short term responders
SA452868CARTG4xUPN209_RPposCAR-T cells Short term responders
SA452869CARTG4xUPN209_RPnegCAR-T cells Short term responders
SA452870CARTG11xUPN397_HILICposCAR-T cells Short term responders
SA452871CARTG11xUPN397_HILICnegCAR-T cells Short term responders
SA452872CARTG3xUPN379_RPposCAR-T cells Short term responders
SA452873CARTG3xUPN379_RPnegCAR-T cells Short term responders
SA452874CARTG2xUPN293_RPposCAR-T cells Short term responders
SA452875CARTG2xUPN293_RPnegCAR-T cells Short term responders
SA452876CARTG5xUPN431_RPposCAR-T cells Short term responders
SA452877CARTG5xUPN431_HILICnegCAR-T cells Short term responders
SA452878CARTG5xUPN431_HILICposCAR-T cells Short term responders
SA452879CARTG3xUPN379_HILICposCAR-T cells Short term responders
SA452880CARTG6xUPN549_HILICnegCAR-T cells Short term responders
SA452881CARTG6xUPN549_HILICposCAR-T cells Short term responders
SA452882CARTG7xUPN466_HILICnegCAR-T cells Short term responders
SA452883CARTG7xUPN466_HILICposCAR-T cells Short term responders
SA452884CARTG4xUPN209_HILICposCAR-T cells Short term responders
SA452885CARTG4xUPN209_HILICnegCAR-T cells Short term responders
SA452886CARTG3xUPN379_HILICnegCAR-T cells Short term responders
SA452887CARTG14xUPN543_RPnegCAR-T cells Short term responders
SA452888CARTG2xUPN293_HILICposCAR-T cells Short term responders
SA452889CARTG2xUPN293_HILICnegCAR-T cells Short term responders
SA452890CARTG11xUPN397_RPnegCAR-T cells Short term responders
SA452891CARTG11xUPN397_RPposCAR-T cells Short term responders
SA452892CARTG14xUPN543_HILICposCAR-T cells Short term responders
SA452893CARTG14xUPN543_HILICnegCAR-T cells Short term responders
SA452894CARTG14xUPN543_RPposCAR-T cells Short term responders
Showing results 1 to 56 of 56

Collection:

Collection ID:CO004093
Collection Summary:De-identified clinical samples were collected from a subset of adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) who received investigational CD19-specific CAR T cells in a phase 1/2 clinical trial (NCT02146924) at City of Hope. For CAR T cells, PBMC were depleted of CD14+ monocytes and CD25+ Tregs, followed by positive selection of CD62L+ T cells. Tcm-derived CAR T cells were purified, transduced, formulated, and released. The CAR T cells were used for metabolomics profiling.
Sample Type:CAR-T cells
Storage Conditions:-80℃

Treatment:

Treatment ID:TR004109
Treatment Summary:Preinfusion CAR-T cells from leukemia patient exhibiting long-term and shor-term treatment response were used for metabolomics profiling.

Sample Preparation:

Sampleprep ID:SP004106
Sampleprep Summary:For CAR-T cells, metabolites were extracted from 3x10^6 cells using of 0.4 mL of solvent mixture (water: methanol: acetonitrile, 1:2.25:0.75, v/v/v) and 3 freeze-thaw (30 seconds each) cycles. The resultant metabolite extracts from CAR T cells were recovered by centrifuging at 13,226 xg at 4°C for 15 min. For HILIC chromatography, the extract was directly used LC-MS analysis. For reversed phase chromatography, the extract was dried under vacuum centrifugation and the dried extract was reconstituted in 20% Acetonitrile, 80% water and used used for LC-MS analysis.
Processing Storage Conditions:-80℃
Extraction Method:The metabolites were extracted using 1 part of water and 3 part of solvent mixture, acetonitrile: methanol (3:1) was added for cell lysis and protein removal
Extract Enrichment:1x
Extract Storage:-80℃
Sample Resuspension:For reversed phase chormatography, the metabolites were reconstituted in water-acetonitrile (80:20, v/v) and for HILIC chromatography, clarified neat extract was sued
Sample Derivatization:none
Sample Spiking:The samples were spiked with isotopically labelled internal standards

Chromatography:

Chromatography ID:CH004946
Chromatography Summary:HILIC chromatography
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um)
Column Temperature:45
Flow Gradient:99% B for 1 min, 99–85% B for 3 min, 85–75% B for 3 min, 75–30% B for 3 min, 30% B for 1 min, 30-99%B for 1 min and 99%B for 4 min
Flow Rate:0.35 ml/min
Injection Temperature:4
Solvent A:95% water/5% acetonitrile; 10mM ammonium acetate; 0.1% acetic acid
Solvent B:95% acetonitrilie/5% water; 10mM ammonium acetate; 0.1% acetic acid
Chromatography Type:HILIC
  
Chromatography ID:CH004947
Chromatography Summary:Reversed phase chromatography
Instrument Name:Thermo Vanquish
Column Name:Thermo Hypersil Gold C18 (150 x 2.1mm, 1.9um)
Column Temperature:45
Flow Gradient:0% B for 1min, 0-50% B for 4 min, 50-98% B for 3 min, 98% B for 2 min, 0% B for 0.5min, 0% B for 5 min
Flow Rate:0.3 ml/min
Injection Temperature:4
Solvent A:100% water; 0.1% formic acid
Solvent B:100% Acetonitrile, 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN006511
Analysis Type:MS
Chromatography ID:CH004946
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003963_AN006511_Results.txt
Units:Peak area
  
Analysis ID:AN006512
Analysis Type:MS
Chromatography ID:CH004946
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003963_AN006512_Results.txt
Units:Peak area
  
Analysis ID:AN006513
Analysis Type:MS
Chromatography ID:CH004947
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003963_AN006513_Results.txt
Units:Peak area
  
Analysis ID:AN006514
Analysis Type:MS
Chromatography ID:CH004947
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003963_AN006514_Results.txt
Units:Peak area
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