Summary of project PR001970
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 PR001970. The data can be accessed directly via it's Project DOI: 10.21228/M8314P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001970 |
| Project DOI: | doi: 10.21228/M8314P |
| Project Title: | Releasing the mitochondrial respiration brake MCJ/DnaJC15 enhances CD8 CAR-T cell therapy efficacy |
| Project Summary: | Metabolism of chimeric antigen receptor (CAR) T cells is emerging as an important area to improve CAR-T cell therapy in cancer treatment. Mitochondrial respiration is essential for survival and function of CAR-T cells, but developing strategies to specifically enhance mitochondrial respiration has been challenging. Here we identify MCJ/DnaJC15, an endogenous negative regulator of mitochondrial Complex I, as a metabolic target to enhance mitochondrial respiration in CD8 CAR-T cells. Loss of MCJ in CD8 CAR-T cells increases their in vitro and in vivo efficacy against mouse B cell leukemias. MCJ deficiency in TCR- specific CD8 cells also increases their efficacy against solid tumors in vivo. Furthermore, we reveal that human CD8 cells express MCJ and that silencing MCJ expression increases mitochondrial metabolism and anti-tumor activity of human CAR-T cells. Thus, targeting MCJ to enhance mitochondrial metabolism is a promising therapeutic strategy to improve the efficacy of adoptive T cell therapies. |
| Institute: | University of Colorado School of Medicine |
| Laboratory: | Laboratory of Angelo D'Alessandro in collaboration with Mercedes Rincon |
| Last Name: | Cendali |
| First Name: | Francesca |
| Address: | 13199 East Montview Boulevard, Aurora, CO, 80045, USA |
| Email: | francesca.cendali@cuanschutz.edu |
| Phone: | 3037246131 |
Summary of all studies in project PR001970
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003166 | Metabolomics of Murine WT or MCJ KO CD19-BBz CD8 CAR-T cells | Mus musculus | University of Colorado School of Medicine | MS | 2024-05-02 | 1 | 8 | Uploaded data (504.6M)* |
| ST003167 | Metabolomics of Human CD19-BBz CD8 CAR-T cells with low and high MCJ expression | Homo sapiens | University of Colorado School of Medicine | MS | 2024-05-02 | 1 | 6 | Uploaded data (106.4M)* |
| ST003169 | Metabolomics of infused Murine WT or MCJ KO CD19-BBz CD8 CAR-T cells from Leukemia-bearing Mice | Mus musculus | University of Colorado School of Medicine | MS | 2024-05-02 | 1 | 6 | Uploaded data (825M)* |
| ST003170 | Metabolomics of Murine WT or MCJ KO CD19-BBz CD8 CAR-T cells rest in medium | Mus musculus | University of Colorado School of Medicine | MS | 2024-05-02 | 1 | 6 | Uploaded data (504.6M)* |
