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.
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 | ST002488 |
Study Title | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - T-cell tracing supernatants |
Study 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 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 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: | SU002578 |
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 | Timepoint |
---|---|---|---|
SA248844 | AG-23-TS-28 | aCD25 | 1 hr |
SA248845 | AG-23-TS-29 | aCD25 | 1 hr |
SA248846 | AG-23-TS-30 | aCD25 | 1 hr |
SA248847 | AG-23-TS-43 | aCD25 | 2 hr |
SA248848 | AG-23-TS-45 | aCD25 | 2 hr |
SA248849 | AG-23-TS-44 | aCD25 | 2 hr |
SA248850 | AG-23-TS-15 | aCD25 | 5 min |
SA248851 | AG-23-TS-13 | aCD25 | 5 min |
SA248852 | AG-23-TS-14 | aCD25 | 5 min |
SA248853 | AG-23-TS-60 | aCD25 | 6 hr |
SA248854 | AG-23-TS-58 | aCD25 | 6 hr |
SA248855 | AG-23-TS-59 | aCD25 | 6 hr |
SA248796 | AG-23-TS-24 | IL2v | 1 hr |
SA248797 | AG-23-TS-23 | IL2v | 1 hr |
SA248798 | AG-23-TS-22 | IL2v | 1 hr |
SA248799 | AG-23-TS-37 | IL2v | 2 hr |
SA248800 | AG-23-TS-38 | IL2v | 2 hr |
SA248801 | AG-23-TS-39 | IL2v | 2 hr |
SA248802 | AG-23-TS-9 | IL2v | 5 min |
SA248803 | AG-23-TS-7 | IL2v | 5 min |
SA248804 | AG-23-TS-8 | IL2v | 5 min |
SA248805 | AG-23-TS-52 | IL2v | 6 hr |
SA248806 | AG-23-TS-53 | IL2v | 6 hr |
SA248807 | AG-23-TS-54 | IL2v | 6 hr |
SA248808 | AG-23-TS-27 | RT+IL2v | 1 hr |
SA248809 | AG-23-TS-25 | RT+IL2v | 1 hr |
SA248810 | AG-23-TS-26 | RT+IL2v | 1 hr |
SA248811 | AG-23-TS-41 | RT+IL2v | 2 hr |
SA248812 | AG-23-TS-42 | RT+IL2v | 2 hr |
SA248813 | AG-23-TS-40 | RT+IL2v | 2 hr |
SA248814 | AG-23-TS-11 | RT+IL2v | 5 min |
SA248815 | AG-23-TS-10 | RT+IL2v | 5 min |
SA248816 | AG-23-TS-12 | RT+IL2v | 5 min |
SA248817 | AG-23-TS-56 | RT+IL2v | 6 hr |
SA248818 | AG-23-TS-57 | RT+IL2v | 6 hr |
SA248819 | AG-23-TS-55 | RT+IL2v | 6 hr |
SA248820 | AG-23-TS-20 | RT | 1 hr |
SA248821 | AG-23-TS-21 | RT | 1 hr |
SA248822 | AG-23-TS-19 | RT | 1 hr |
SA248823 | AG-23-TS-36 | RT | 2 hr |
SA248824 | AG-23-TS-34 | RT | 2 hr |
SA248825 | AG-23-TS-35 | RT | 2 hr |
SA248826 | AG-23-TS-5 | RT | 5 min |
SA248827 | AG-23-TS-4 | RT | 5 min |
SA248828 | AG-23-TS-6 | RT | 5 min |
SA248829 | AG-23-TS-49 | RT | 6 hr |
SA248830 | AG-23-TS-51 | RT | 6 hr |
SA248831 | AG-23-TS-50 | RT | 6 hr |
SA248832 | AG-23-TS-17 | Untrx | 1 hr |
SA248833 | AG-23-TS-18 | Untrx | 1 hr |
SA248834 | AG-23-TS-16 | Untrx | 1 hr |
SA248835 | AG-23-TS-31 | Untrx | 2 hr |
SA248836 | AG-23-TS-33 | Untrx | 2 hr |
SA248837 | AG-23-TS-32 | Untrx | 2 hr |
SA248838 | AG-23-TS-1 | Untrx | 5 min |
SA248839 | AG-23-TS-3 | Untrx | 5 min |
SA248840 | AG-23-TS-2 | Untrx | 5 min |
SA248841 | AG-23-TS-48 | Untrx | 6 hr |
SA248842 | AG-23-TS-46 | Untrx | 6 hr |
SA248843 | AG-23-TS-47 | Untrx | 6 hr |
Showing results 1 to 60 of 60 |
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 |