Summary of Study ST003965

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 IDST003965
Study TitleImmunometabolic determinants of long-term response in leukapheresis T cells of the leukemia patients receiving CD19 CAR T cell therapy
Study TypeUntargeted metabolomics
Study SummaryTo understand the immunometabolic features of T cells conferring long-term response in leukemia patients, we investigated metabolome of leukapheresis T cells isolated from both long-term and short-term responders. We observed significant difference in the T cell metabolome of long-term vs short-term responders suggesting that metabolism in native Tcell has potential influence on antileukemic activity of CAR-T cells.
Institute
Translational Genomics Research Institute
Last NamePirrotte
First NamePatrick
Address445 N 5TH STREET
Emailims@tgen.org
Phone16023438454
Submit Date2025-06-02
Num Females8
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:SU004102
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
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
SA452943LT12xTnmem518_RPposleukapheresis T cells Long-term responders
SA452944LT9xTnmem505_HILICnegleukapheresis T cells Long-term responders
SA452945LT9xTnmem505_HILICposleukapheresis T cells Long-term responders
SA452946LT10xTnmem495_HILICposleukapheresis T cells Long-term responders
SA452947LT10xTnmem495_RPposleukapheresis T cells Long-term responders
SA452948LT11xTnmem188_RPnegleukapheresis T cells Long-term responders
SA452949LT11xTnmem188_RPposleukapheresis T cells Long-term responders
SA452950LT12xTnmem518_RPnegleukapheresis T cells Long-term responders
SA452951LT13xTnmem544_RPnegleukapheresis T cells Long-term responders
SA452952LT8xTnmem245_HILICnegleukapheresis T cells Long-term responders
SA452953LT13xTnmem544_RPposleukapheresis T cells Long-term responders
SA452954LT14xTnmem552_RPnegleukapheresis T cells Long-term responders
SA452955LT14xTnmem552_RPposleukapheresis T cells Long-term responders
SA452956LT8xTnmem245_RPnegleukapheresis T cells Long-term responders
SA452957LT8xTnmem245_RPposleukapheresis T cells Long-term responders
SA452958LT9xTnmem505_RPnegleukapheresis T cells Long-term responders
SA452959LT9xTnmem505_RPposleukapheresis T cells Long-term responders
SA452960LT8xTnmem245_HILICposleukapheresis T cells Long-term responders
SA452961LT10xTnmem495_HILICnegleukapheresis T cells Long-term responders
SA452962LT10xTnmem495_RPnegleukapheresis T cells Long-term responders
SA452963LT11xTnmem188_HILICnegleukapheresis T cells Long-term responders
SA452964LT11xTnmem188_HILICposleukapheresis T cells Long-term responders
SA452965LT12xTnmem518_HILICnegleukapheresis T cells Long-term responders
SA452966LT12xTnmem518_HILICposleukapheresis T cells Long-term responders
SA452967LT13xTnmem544_HILICnegleukapheresis T cells Long-term responders
SA452968LT13xTnmem544_HILICposleukapheresis T cells Long-term responders
SA452969LT14xTnmem552_HILICnegleukapheresis T cells Long-term responders
SA452970LT14xTnmem552_HILICposleukapheresis T cells Long-term responders
SA452971LT4xTnmem379_RPnegleukapheresis T cells Short-term responders
SA452972LT3xTnmem431_RPposleukapheresis T cells Short-term responders
SA452973LT5xTnmem293_RPposleukapheresis T cells Short-term responders
SA452974LT4xTnmem379_RPposleukapheresis T cells Short-term responders
SA452975LT5xTnmem293_RPnegleukapheresis T cells Short-term responders
SA452976LT2xTnmem466_RPposleukapheresis T cells Short-term responders
SA452977LT6xTnmem543_RPnegleukapheresis T cells Short-term responders
SA452978LT6xTnmem543_RPposleukapheresis T cells Short-term responders
SA452979Lt7xTnmem549_RPnegleukapheresis T cells Short-term responders
SA452980Lt7xTnmem549_RPposleukapheresis T cells Short-term responders
SA452981LT3xTnmem431_RPnegleukapheresis T cells Short-term responders
SA452982LT6xTnmem543_HILICnegleukapheresis T cells Short-term responders
SA452983LT2xTnmem466_RPnegleukapheresis T cells Short-term responders
SA452984LT1xTnmem209_RPposleukapheresis T cells Short-term responders
SA452985LT6xTnmem543_HILICposleukapheresis T cells Short-term responders
SA452986LT1xTnmem209_HILICnegleukapheresis T cells Short-term responders
SA452987LT1xTnmem209_HILICposleukapheresis T cells Short-term responders
SA452988LT2xTnmem466_HILICnegleukapheresis T cells Short-term responders
SA452989LT2xTnmem466_HILICposleukapheresis T cells Short-term responders
SA452990LT3xTnmem431_HILICnegleukapheresis T cells Short-term responders
SA452991LT3xTnmem431_HILICposleukapheresis T cells Short-term responders
SA452992LT4xTnmem379_HILICnegleukapheresis T cells Short-term responders
SA452993LT4xTnmem379_HILICposleukapheresis T cells Short-term responders
SA452994LT5xTnmem293_HILICnegleukapheresis T cells Short-term responders
SA452995LT5xTnmem293_HILICposleukapheresis T cells Short-term responders
SA452996Lt7xTnmem549_HILICposleukapheresis T cells Short-term responders
SA452997Lt7xTnmem549_HILICnegleukapheresis T cells Short-term responders
SA452998LT1xTnmem209_RPnegleukapheresis T cells Short-term responders
Showing results 1 to 56 of 56

Collection:

Collection ID:CO004095
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. Patient or donor's Tcells were collected by leukapheresis. The leukapheresis Tcells were used for metabolomics profiling.
Sample Type:T-cells
Storage Conditions:-80℃

Treatment:

Treatment ID:TR004111
Treatment Summary:Tn/mem cells were enriched from leukapheresis from long-term and short-term responders were used for the study

Sample Preparation:

Sampleprep ID:SP004108
Sampleprep Summary:For leukapheresis T cells, metabolites were extracted using 0.4 mL 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 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℃
Extract Storage:-80℃

Chromatography:

Chromatography ID:CH004950
Chromatography Summary:HILIC Chromatography
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC BEH HILIC (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
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:CH004951
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
Solvent A:100% Water; 0.1% formic acid
Solvent B:100% Acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN006519
Analysis Type:MS
Chromatography ID:CH004950
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003965_AN006519_Results.txt
Units:Peak area
  
Analysis ID:AN006520
Analysis Type:MS
Chromatography ID:CH004950
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003965_AN006520_Results.txt
Units:Peak area
  
Analysis ID:AN006521
Analysis Type:MS
Chromatography ID:CH004951
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003965_AN006521_Results.txt
Units:Peak area
  
Analysis ID:AN006522
Analysis Type:MS
Chromatography ID:CH004951
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003965_AN006522_Results.txt
Units:Peak area
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