Summary of project PR002483
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 PR002483. The data can be accessed directly via it's Project DOI: 10.21228/M8PJ91 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002483 |
| Project DOI: | doi: 10.21228/M8PJ91 |
| Project Title: | Metabolomics of CAR-T cells and their products in leukemia patients |
| Project Type: | Untargeted metabolomics |
| Project Summary: | Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. We applied an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) had increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR had high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induced metabolic reprogramming and enhanced anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission. |
| Institute: | Translational Genomics Research Institute |
| Last Name: | Pirrotte |
| First Name: | Patrick |
| Address: | 445 N 5TH STREET, Phoenix, Arizona |
| Email: | ims@tgen.org |
| Phone: | 6023438454 |
| Funding Source: | NIH K12 grant no. 5K12CA001727–29, The Hyundai Hope on Wheels Young Investigator Award, NCI grant no.P30CA033572 |
| Project Comments: | Study 1 of 4 |
| Contributors: | Lior Goldberg, Eric R. Haas, Jiaqi Wu, Bryan Garcia, Ryan Urak, Vibhuti Vyas, Ruby Espinosa, Tamara Munoz, Shirley Bierkatz, Jamie R. Wagner, Jinny Paul, Mary C. Clark, Dat Ngo, Ibrahim Aldoss, Stephen J. Forman & Xiuli Wang |
Summary of all studies in project PR002483
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003963 | Immunometabolic determinants of long-term response in preinfusion CAR-T cells of the leukemia patients receiving CD19 CAR T cell therapy | Homo sapiens | Translational Genomics Research Institute | MS* | 2025-07-07 | 1 | 56 | Uploaded data (5.4G)* |
| ST003964 | Immunometabolism determinants of enhanced antileukemic activity upon rapamycin mediated mTOR inhibition in CAR-T cells of short-term responder leukemia patients receiving CD19 CAR T cell therapy | Homo sapiens | Translational Genomics Research Institute | MS* | 2025-07-07 | 1 | 48 | Uploaded data (5.9G)* |
| ST003965 | Immunometabolic determinants of long-term response in leukapheresis T cells of the leukemia patients receiving CD19 CAR T cell therapy | Homo sapiens | Translational Genomics Research Institute | MS* | 2025-07-07 | 1 | 56 | Uploaded data (6.8G)* |
| ST003966 | Immunometabolic determinants of long-term response in bone marrow of the leukemia patients receiving CD19 CAR T cell therapy | Homo sapiens | Translational Genomics Research Institute | MS* | 2025-07-07 | 1 | 64 | Uploaded data (6.8G)* |
