Summary of Study ST002488

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 IDST002488
Study TitleSimultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - T-cell tracing supernatants
Study SummaryC57BL/6 mice were orthotopically implanted with PK5L1940 cells. 8 Gy RT was administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Spleens and lymph nodes were harvested 17 days post implantation and the sorted T-cells cultured in the presence of 13C6 glucose for 6h. This study contains longitudinal sampling of the cell culture supernatants.
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:SU002578
Subject Type:Mammal
Subject Species:Mus musculus

Factors:

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

mb_sample_id local_sample_id Factor Timepoint
SA248844AG-23-TS-28aCD25 1 hr
SA248845AG-23-TS-29aCD25 1 hr
SA248846AG-23-TS-30aCD25 1 hr
SA248847AG-23-TS-43aCD25 2 hr
SA248848AG-23-TS-45aCD25 2 hr
SA248849AG-23-TS-44aCD25 2 hr
SA248850AG-23-TS-15aCD25 5 min
SA248851AG-23-TS-13aCD25 5 min
SA248852AG-23-TS-14aCD25 5 min
SA248853AG-23-TS-60aCD25 6 hr
SA248854AG-23-TS-58aCD25 6 hr
SA248855AG-23-TS-59aCD25 6 hr
SA248796AG-23-TS-24IL2v 1 hr
SA248797AG-23-TS-23IL2v 1 hr
SA248798AG-23-TS-22IL2v 1 hr
SA248799AG-23-TS-37IL2v 2 hr
SA248800AG-23-TS-38IL2v 2 hr
SA248801AG-23-TS-39IL2v 2 hr
SA248802AG-23-TS-9IL2v 5 min
SA248803AG-23-TS-7IL2v 5 min
SA248804AG-23-TS-8IL2v 5 min
SA248805AG-23-TS-52IL2v 6 hr
SA248806AG-23-TS-53IL2v 6 hr
SA248807AG-23-TS-54IL2v 6 hr
SA248808AG-23-TS-27RT+IL2v 1 hr
SA248809AG-23-TS-25RT+IL2v 1 hr
SA248810AG-23-TS-26RT+IL2v 1 hr
SA248811AG-23-TS-41RT+IL2v 2 hr
SA248812AG-23-TS-42RT+IL2v 2 hr
SA248813AG-23-TS-40RT+IL2v 2 hr
SA248814AG-23-TS-11RT+IL2v 5 min
SA248815AG-23-TS-10RT+IL2v 5 min
SA248816AG-23-TS-12RT+IL2v 5 min
SA248817AG-23-TS-56RT+IL2v 6 hr
SA248818AG-23-TS-57RT+IL2v 6 hr
SA248819AG-23-TS-55RT+IL2v 6 hr
SA248820AG-23-TS-20RT 1 hr
SA248821AG-23-TS-21RT 1 hr
SA248822AG-23-TS-19RT 1 hr
SA248823AG-23-TS-36RT 2 hr
SA248824AG-23-TS-34RT 2 hr
SA248825AG-23-TS-35RT 2 hr
SA248826AG-23-TS-5RT 5 min
SA248827AG-23-TS-4RT 5 min
SA248828AG-23-TS-6RT 5 min
SA248829AG-23-TS-49RT 6 hr
SA248830AG-23-TS-51RT 6 hr
SA248831AG-23-TS-50RT 6 hr
SA248832AG-23-TS-17Untrx 1 hr
SA248833AG-23-TS-18Untrx 1 hr
SA248834AG-23-TS-16Untrx 1 hr
SA248835AG-23-TS-31Untrx 2 hr
SA248836AG-23-TS-33Untrx 2 hr
SA248837AG-23-TS-32Untrx 2 hr
SA248838AG-23-TS-1Untrx 5 min
SA248839AG-23-TS-3Untrx 5 min
SA248840AG-23-TS-2Untrx 5 min
SA248841AG-23-TS-48Untrx 6 hr
SA248842AG-23-TS-46Untrx 6 hr
SA248843AG-23-TS-47Untrx 6 hr
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Collection:

Collection ID:CO002571
Collection Summary:C57BL/6 mice were orthotopically implanted with PK5L1940 cells. 8 Gy RT was administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Spleens and lymph nodes were harvested 17 days post implantation and homogenized to a single cell suspension by mashing through a 70 uM cell strainer. For spleen processing, the erythrocytes were lysed with ACK (ammonium-chloride-potassium) lysis buffer for 3 min at RT. CD8 T cells were sorted with a CD8-negative selection Stemcell isolation kit following manufacturer instructions.
Sample Type:Cell culture supernatant

Treatment:

Treatment ID:TR002590
Treatment Summary:CD8+ T cells were cultured for 6h in the presence of 25 mM U-13C-glucose in glucose-free RPMI. Media aliquots were taken at 5 min, 1h, 2h, 6h and snap frozen.

Sample Preparation:

Sampleprep ID:SP002584
Sampleprep Summary:Supernatant 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 AN004062
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode NEGATIVE
Units peak area

Chromatography:

Chromatography ID:CH003008
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

MS:

MS ID:MS003809
Analysis ID:AN004062
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
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