The effectiveness of adoptive T cell therapies is tightly regulated by the content and activity of mitochondria, which reside within cells and are responsible for producing the majority of a cell’s energy. Loss of mitochondrial function in T cells has been shown to be associated with poor cell proliferation and persistence as well as decreased anti-tumor activity. Emerging evidence has recently demonstrated that mitochondria are not fixed within an individual cell but can travel to adjacent cells via a process known as mitochondrial transfer, in which membrane-based extensions form connections and traffic mitochondria from one cell to another.
Seminal work by Dr. Gattinoni’s group showed that mesenchymal stem cells (MSC) are capable of transferring their mitochondria to killer T cells, and that these killer T cells with donated mitochondria have improved metabolic activity, enhanced anti-tumor activity, and are associated with improved cancer survival rates in preclinical models. Now, Dr. Gattinoni is focused on developing this research further as a broad platform technology for enhancing the metabolic fitness and cancer-killing capabilities of adoptive T cells in order to improve the clinical outcomes of cancer immunotherapies.
Projects and Grants
Mitochondrial Transfer: A Novel Technology Platform for Enhancing the Metabolic Fitness and Anti-Tumor Efficacy of Adoptive T Cell Therapies
Regensburg Center for Interventional Immunology (Germany) | All Cancers | 2020
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