Summary of Study ST002485

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 PR001607. The data can be accessed directly via it's Project DOI: 10.21228/M8013C This work is supported by NIH grant, U2C- DK119886.

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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 IDST002485
Study TitleSimultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse serum metabolomics
Study SummaryMice were orthotopically implanted with PK5L1940 cells then radiation therapy (8 Gy) administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Serum was collected at time of sacrifice and profiled by mass spectrometry-based metabolomics to visualize changes in systemic metabolism in the mouse model.
Institute
University of Colorado Denver
Last NameHaines
First NameJulie
Address12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
Emailjulie.haines@cuanschutz.edu
Phone3037243339
Submit Date2023-02-21
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-03-10
Release Version1
Julie Haines Julie Haines
https://dx.doi.org/10.21228/M8013C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001607
Project DOI:doi: 10.21228/M8013C
Project Title:Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis
Project Summary:In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL2Rβ and IL2Rγ and decreased ILR2α expression. The bispecific aPD1-IL2v is a PD-1-targeted IL-2 variant (IL2v) immunocytokine with engineered IL-2 cis-targeted to PD-1 and abolished IL2Rα binding, which enhances tumor-antigen specific T cell activation while reducing regulatory T cell (Treg) suppression. Using aPD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival along with profound increase in tumor-infiltrating polyfunctional CD8+ T cell subsets with a transcriptionally and metabolically active phenotype, and preferential activation of antigen-specific CD8+ T cells. In combination with single dose RT, aPD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8+ T cells, T cell stemness, tumor-specific memory immune response, natural killer (NK) cell activation, and decreased Tregs. These data show that aPD1-IL2v leads to profound local and distant response in PDAC.
Institute:University of Colorado Denver
Laboratory:Lab of Angelo D'Alessandro in collaboration with lab of Sana Karam
Last Name:Haines
First Name:Julie
Address:12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
Email:julie.haines@cuanschutz.edu
Phone:3037243339

Subject:

Subject ID:SU002575
Subject Type:Mammal
Subject Species:Mus musculus
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id treatment
SA2487541RT
SA2487553RT
SA2487562RT
SA2487604RT+aCD25
SA2487616RT+aCD25
SA2487625RT+aCD25
SA24876312RT+aCD25+IL2v
SA24876410RT+aCD25+IL2v
SA24876511RT+aCD25+IL2v
SA2487578RT+IL2v
SA2487589RT+IL2v
SA2487597RT+IL2v
Showing results 1 to 12 of 12

Collection:

Collection ID:CO002568
Collection Summary:Blood was collected at the time of sacrifice via cardiac puncture. Serum was isolated using BD microcontainer plasma separation collection tubes. Serum layer was harvested after centrifugation at 6000RPM, 4degC for 2mins, and flash frozen.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR002587
Treatment Summary:Mice were orthotopically implanted with PK5L1940 cells. RT administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Serum collected at time of sacrifice.

Sample Preparation:

Sampleprep ID:SP002581
Sampleprep Summary:Serum aliquots were thawed on ice then a 20 uL aliquot treated with 480 uL of cold 5:3:2 MeOH:acetonitrile:water. Samples were vortexed 30 min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000 g, 4 degrees C) and transferred to autosampler vials.
Processing Storage Conditions:4℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN004056 AN004057
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode NEGATIVE POSITIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH003002
Chromatography Summary:Negative C18
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um
Column Temperature:45
Flow Gradient:0-0.5 min 0% B, 0.5-1.1 min 0-100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min 100-0% B, 3-5 min hold at 0% B
Flow Rate:450 uL/min
Sample Injection:10 uL
Solvent A:95% water 5% acetonitrile 1 mM ammonium acetate
Solvent B:95% acetonitrile 5% water 1 mM ammonium acetate
Chromatography Type:Reversed phase
  
Chromatography ID:CH003003
Chromatography Summary:Positive C18
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um
Column Temperature:45
Flow Gradient:0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min 95-5% B, 3-5 min hold at 5% B
Flow Rate:450 uL/min
Sample Injection:10 uL
Solvent A:100% water; 0.1% formic acid
Solvent B:100%acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003803
Analysis ID:AN004056
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms, microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV, capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas 0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were annotated and integrated using Maven in conjunction with the KEGG database.
Ion Mode:NEGATIVE
  
MS ID:MS003804
Analysis ID:AN004057
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms, microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV, capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas 0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were annotated and integrated using Maven in conjunction with the KEGG database.
Ion Mode:POSITIVE
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