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 |
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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 |