Summary of project PR001607
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
| 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 |
Summary of all studies in project PR001607
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002485 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse serum metabolomics | Mus musculus | University of Colorado Denver | MS | 2023-03-10 | 1 | 12 | Uploaded data (892.5M)* |
| ST002486 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse blood T-cell metabolomics | Mus musculus | University of Colorado Denver | MS | 2023-03-10 | 1 | 15 | Uploaded data (1.6G)* |
| ST002487 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse spleen and lymph node T-cell metabolomics | Mus musculus | University of Colorado Denver | MS | 2023-03-10 | 1 | 15 | Uploaded data (1.6G)* |
| ST002488 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - T-cell tracing supernatants | Mus musculus | University of Colorado Denver | MS | 2023-03-10 | 1 | 60 | Uploaded data (1.9G)* |
| ST002489 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis | Mus musculus | University of Colorado Denver | MS | 2023-03-10 | 1 | 15 | Uploaded data (355.2M)* |
| ST002490 | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - human plasma metabolomics | Homo sapiens | University of Colorado Denver | MS | 2023-03-10 | 1 | 35 | Uploaded data (1.8G)* |
