Summary of Study ST003966

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

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Study IDST003966
Study TitleImmunometabolic determinants of long-term response in bone marrow of the leukemia patients receiving CD19 CAR T cell therapy
Study TypeUntargeted metabolomics
Study SummaryTo study relationship between immunometabolism and CAR T cell anti-tumor activity in patients, we examined bone marrow samples 28th day post CAR-T cell treatment. By looking into patients' bone marrow metabolome using untargeted metabolomics allowed us to investigate the microenvironment of both leukemia and post-infusion CAR-T cells. We identified that bone marrow metabolome was significantly different between long-term and short-term responders where bone marrow of long-term responders had significantly higher amino acid pool, lactic acid and inosine compared to short-term responders further the CAR-T cells in bone marrow also had acquired distinct metabolic state post infusion. The study identified metabolic composition of microenvironment has significant role in efficacy of CAR-T therapy.
Institute
Translational Genomics Research Institute
Last NamePirrotte
First NamePatrick
Address445 N 5th St, Phoenix, Arizona
Emailims@tgen.org
Phone16023438454
Submit Date2025-06-02
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:SU004103
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
SA452999413SBM4LTR_RPposBone marrow serum Long-term responders
SA453000544SBM8LTR_HILICposBone marrow serum Long-term responders
SA453001552SBM1LTR_HILICnegBone marrow serum Long-term responders
SA453002552SBM1LTR_HILICposBone marrow serum Long-term responders
SA453003188SBM2LTR_HILICposBone marrow serum Long-term responders
SA453004188SBM2LTR_RPposBone marrow serum Long-term responders
SA453005245SBM3LTR_RPnegBone marrow serum Long-term responders
SA453006245SBM3LTR_RPposBone marrow serum Long-term responders
SA453007413SBM4LTR_RPnegBone marrow serum Long-term responders
SA453008495SBM5LTR_RPnegBone marrow serum Long-term responders
SA453009518SBM7LTR_HILICposBone marrow serum Long-term responders
SA453010495SBM5LTR_RPposBone marrow serum Long-term responders
SA453011505SBM6LTR_RPnegBone marrow serum Long-term responders
SA453012505SBM6LTR_RPposBone marrow serum Long-term responders
SA453013518SBM7LTR_RPnegBone marrow serum Long-term responders
SA453014518SBM7LTR_RPposBone marrow serum Long-term responders
SA453015544SBM8LTR_RPnegBone marrow serum Long-term responders
SA453016544SBM8LTR_RPposBone marrow serum Long-term responders
SA453017552SBM1LTR_RPnegBone marrow serum Long-term responders
SA453018552SBM1LTR_RPposBone marrow serum Long-term responders
SA453019544SBM8LTR_HILICnegBone marrow serum Long-term responders
SA453020188SBM2LTR_HILICnegBone marrow serum Long-term responders
SA453021518SBM7LTR_HILICnegBone marrow serum Long-term responders
SA453022495SBM5LTR_HILICposBone marrow serum Long-term responders
SA453023245SBM3LTR_HILICnegBone marrow serum Long-term responders
SA453024245SBM3LTR_HILICposBone marrow serum Long-term responders
SA453025413SBM4LTR_HILICnegBone marrow serum Long-term responders
SA453026495SBM5LTR_HILICnegBone marrow serum Long-term responders
SA453027413SBM4LTR_HILICposBone marrow serum Long-term responders
SA453028188SBM2LTR_RPnegBone marrow serum Long-term responders
SA453029505SBM6LTR_HILICnegBone marrow serum Long-term responders
SA453030505SBM6LTR_HILICposBone marrow serum Long-term responders
SA453031293SBM9STR_HILICnegBone marrow serum Short term responders
SA453032397SBM12STR_HILICnegBone marrow serum Short term responders
SA453033379SBM11STR_HILICposBone marrow serum Short term responders
SA453034379SBM11STR_HILICnegBone marrow serum Short term responders
SA453035293SBM9STR_HILICposBone marrow serum Short term responders
SA453036543SBM15STR_RPposBone marrow serum Short term responders
SA453037543SBM15STR_RPnegBone marrow serum Short term responders
SA453038466SBM14STR_RPposBone marrow serum Short term responders
SA453039543SBM15STR_HILICposBone marrow serum Short term responders
SA453040549SBM16STR_RPnegBone marrow serum Short term responders
SA453041549SBM16STR_RPposBone marrow serum Short term responders
SA453042209SBM10STR_HILICposBone marrow serum Short term responders
SA453043209SBM10STR_HILICnegBone marrow serum Short term responders
SA453044397SBM12STR_HILICposBone marrow serum Short term responders
SA453045549SBM16STR_HILICposBone marrow serum Short term responders
SA453046466SBM14STR_RPnegBone marrow serum Short term responders
SA453047293SBM9STR_RPnegBone marrow serum Short term responders
SA453048466SBM14STR_HILICposBone marrow serum Short term responders
SA453049466SBM14STR_HILICnegBone marrow serum Short term responders
SA453050209SBM10STR_RPnegBone marrow serum Short term responders
SA453051209SBM10STR_RPposBone marrow serum Short term responders
SA453052431SBM13STR_HILICposBone marrow serum Short term responders
SA453053431SBM13STR_HILICnegBone marrow serum Short term responders
SA453054293SBM9STR_RPposBone marrow serum Short term responders
SA453055549SBM16STR_HILICnegBone marrow serum Short term responders
SA453056379SBM11STR_RPnegBone marrow serum Short term responders
SA453057379SBM11STR_RPposBone marrow serum Short term responders
SA453058397SBM12STR_RPnegBone marrow serum Short term responders
SA453059397SBM12STR_RPposBone marrow serum Short term responders
SA453060543SBM15STR_HILICnegBone marrow serum Short term responders
SA453061431SBM13STR_RPnegBone marrow serum Short term responders
SA453062431SBM13STR_RPposBone marrow serum Short term responders
Showing results 1 to 64 of 64

Collection:

Collection ID:CO004096
Collection Summary:Bone marrow serum (post-infusion CAR T cells in bone marrow) was collected 28day post CAR-T cell infusion in leukemia patients
Sample Type:Serum of bone marrow
Storage Conditions:-80℃

Treatment:

Treatment ID:TR004112
Treatment Summary:The patients were treated with CAR-T cells and after 28th day post infusion they achieved the complete remission.

Sample Preparation:

Sampleprep ID:SP004109
Sampleprep Summary:For bonemarrow, 3-fold excess acetonitrile: methanol (3:1) was added for protein removal. The resultant metabolite extracts from bone marrow 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℃

Combined analysis:

Analysis ID AN006523 AN006524 AN006525 AN006526
Chromatography ID CH004952 CH004952 CH004953 CH004953
MS ID MS006222 MS006223 MS006224 MS006225
Analysis type MS MS MS MS
Chromatography type HILIC HILIC Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish Thermo Vanquish Thermo Vanquish
Column Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um) Thermo Hypersil Gold C18 (150 x 2.1mm, 1.9um) Thermo Hypersil Gold C18 (150 x 2.1mm, 1.9um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Orbitrap Fusion Lumos Tribrid Thermo Orbitrap Fusion Lumos Tribrid Thermo Orbitrap Fusion Lumos Tribrid Thermo Orbitrap Fusion Lumos Tribrid
Ion Mode POSITIVE NEGATIVE NEGATIVE POSITIVE
Units Peak area Peak area Peak area Peak area

Chromatography:

Chromatography ID:CH004952
Chromatography Summary:HILIC
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
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:CH004953
Chromatography Summary:RP
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

MS:

MS ID:MS006222
Analysis ID:AN006523
Instrument Name:Thermo Orbitrap Fusion Lumos Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Xcalibur Compound Discoverer 3.2
Ion Mode:POSITIVE
  
MS ID:MS006223
Analysis ID:AN006524
Instrument Name:Thermo Orbitrap Fusion Lumos Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Xcalibur Compound Discoverer 3.2
Ion Mode:NEGATIVE
  
MS ID:MS006224
Analysis ID:AN006525
Instrument Name:Thermo Orbitrap Fusion Lumos Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Xcalibur Compound Discoverer 3.2
Ion Mode:NEGATIVE
  
MS ID:MS006225
Analysis ID:AN006526
Instrument Name:Thermo Orbitrap Fusion Lumos Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Xcalibur Compound Discoverer 3.2
Ion Mode:POSITIVE
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