Summary of Study ST002490

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 IDST002490
Study TitleSimultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - human plasma metabolomics
Study SummaryPatient plasma samples were collected as part of a Phase I radiation dose-escalation clinical trial (NCT02873598) before, during (6 hours post), and post (6 weeks) SBRT. Samples were collected and analyzed per COMIRB19–0328 for branched chain amino acids and kynurenine.
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:SU002580
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Patient ID Timepoint
SA2488711C04 Baseline
SA2488722C04 During
SA2488733C04 Post
SA2488744C05 Baseline
SA2488755C05 During
SA2488766C05 Post
SA2488777C06 Baseline
SA2488788C06 During
SA2488799C06 Post
SA24888010C08 Baseline
SA24888111C08 During
SA24888212C08 Post
SA24888313C09 Baseline
SA24888414C09 During
SA24888515C09 Post
SA24888616C10 Baseline
SA24888717C10 During
SA24888818C10 Post
SA24888919C11 Baseline
SA24889020C11 During
SA24889121C11 Post
SA24889222C13 Baseline
SA24889323C13 During
SA24889424C13 Post
SA24889525C14 Baseline
SA24889626C14 During
SA24889727C14 Post
SA24889828C15 Baseline
SA24889929C15 During
SA24890030C15 Post
SA24890131C16 Baseline
SA24890232C16 During
SA24890333C16 Post
SA24890434C17 Baseline
SA24890535C17 During
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Collection:

Collection ID:CO002573
Collection Summary:Patient plasma samples were collected as part of a Phase I radiation dose-escalation clinical trial (NCT02873598) before, during (6 hours post), and post (6 weeks) SBRT. Samples were collected and analyzed per COMIRB19–0328.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR002592
Treatment Summary:All patients received neoadjuvant chemotherapy prior to SBRT. SBRT doses ranged from 9Gy × 3 fractions to 11Gy ×3 fractions.

Sample Preparation:

Sampleprep ID:SP002586
Sampleprep Summary:Plasma 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 AN004064
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 POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH003010
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:MS003811
Analysis ID:AN004064
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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