Summary of Study ST002489

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 IDST002489
Study TitleSimultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis
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. T-cells from spleen were obtained through sorting, cultured in the presence of 13C6 glucose for 6h, and glucose fluxes profiled via mass spectrometry-based metabolomics.
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:SU002579
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 factor
SA248865AG-23-TC-15aCD25
SA248866AG-23-TC-14aCD25
SA248867AG-23-TC-13aCD25
SA248856AG-23-TC-9IL2v
SA248857AG-23-TC-7IL2v
SA248858AG-23-TC-8IL2v
SA248859AG-23-TC-5RT
SA248860AG-23-TC-4RT
SA248861AG-23-TC-6RT
SA248862AG-23-TC-11RT+IL2v
SA248863AG-23-TC-12RT+IL2v
SA248864AG-23-TC-10RT+IL2v
SA248868AG-23-TC-2unx
SA248869AG-23-TC-1unx
SA248870AG-23-TC-3unx
Showing results 1 to 15 of 15

Collection:

Collection ID:CO002572
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 of C57BL/6 mice were harvested 17 days post implantation and homogenized to a single cell suspension by mashing through a 70 uM cells strainer. For spleen processing, and the erythrocytes were lysed with ACK (ammonium-chloride-potassium) lysis buffer for 5 min at RT. CD8 T cells were sorted with a CD8-negative selection Stemcell isolation kit following manufacturer instructions.
Sample Type:T-cells

Treatment:

Treatment ID:TR002591
Treatment Summary:CD8+ T cells were cultured for 6h in the presence of 25 mM U-13C-glucose in glucose-free RPMI. Cells were washed in PBS at 1200RPM, 4degC for 10 minutes and pellets were flash frozen.

Sample Preparation:

Sampleprep ID:SP002585
Sampleprep Summary:Metabolites from frozen T-cell pellets were extracted with cold 5:3:2 MeOH:acetonitrile:water at a concentration of 4e6 cells/ml. 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℃

Chromatography:

Chromatography ID:CH003009
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

Analysis:

Analysis ID:AN004063
Analysis Type:MS
Chromatography ID:CH003009
Num Factors:5
Num Metabolites:27
Units:peak area
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