Summary of Study ST002486
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.
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.
| Study ID | ST002486 |
| Study Title | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse blood T-cell metabolomics |
| Study Summary | Mice 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. Blood was collected at time of sacrifice and sorted for CD8+ T-cells. The obtained T-cells were profiled by mass spectrometry-based metabolomics. |
| Institute | University of Colorado Denver |
| Last Name | Haines |
| First Name | Julie |
| Address | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| julie.haines@cuanschutz.edu | |
| Phone | 3037243339 |
| Submit Date | 2023-02-21 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-03-10 |
| Release Version | 1 |
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: | SU002576 |
| 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 |
|---|---|---|
| SA248778 | MB-15 | aCD25 |
| SA248779 | MB-13 | aCD25 |
| SA248780 | MB-14 | aCD25 |
| SA248766 | MB-9 | IL2v |
| SA248767 | MB-7 | IL2v |
| SA248768 | MB-8 | IL2v |
| SA248769 | MB-5 | RT |
| SA248770 | MB-4 | RT |
| SA248771 | MB-6 | RT |
| SA248772 | MB-11 | RT+IL2v |
| SA248773 | MB-12 | RT+IL2v |
| SA248774 | MB-10 | RT+IL2v |
| SA248775 | MB-2 | Untrx |
| SA248776 | MB-3 | Untrx |
| SA248777 | MB-1 | Untrx |
| Showing results 1 to 15 of 15 |
Collection:
| Collection ID: | CO002569 |
| Collection Summary: | Blood was collected at the time of sacrifice via cardiac puncture. The erythrocytes were lysed with ACK lysis buffer for 3min at RT. CD8 T cells were sorted with a CD8-negative selection Stemcell isolation kit according to manufacturer's instructions. Cells were washed with PBS at 1200RPM, 4degC for 10 mins, and cell pellets were flash frozen. |
| Sample Type: | T-cells |
Treatment:
| Treatment ID: | TR002588 |
| Treatment Summary: | Mice were orthotopically implanted with PK5L1940 cells. Radiation therapy (8 Gy) administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Blood collected at time of sacrifice. |
Sample Preparation:
| Sampleprep ID: | SP002582 |
| Sampleprep Summary: | Metabolites from frozen T-cell pellets were extracted with cold 5:3:2 MeOH:acetonitrile:water at a concentration of 4 million 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: | CH003004 |
| 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: | CH003005 |
| 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 |
Analysis:
| Analysis ID: | AN004058 |
| Analysis Type: | MS |
| Chromatography ID: | CH003004 |
| Num Factors: | 5 |
| Num Metabolites: | 73 |
| Units: | peak area |
| Analysis ID: | AN004059 |
| Analysis Type: | MS |
| Chromatography ID: | CH003005 |
| Num Factors: | 5 |
| Num Metabolites: | 57 |
| Units: | peak area |
