Stem cells provide T cells a lifeline as cancer champions

In a pioneering study that bridges the gap between science fiction and reality, researchers have unveiled an innovative method to enhance T and CAR-T cells—our body’s natural and engineered defenders against cancer—by providing them with a mitochondrial supercharge.

CAR-T cells are engineered immune cells that are modified to express receptors that specifically target and attack cancer cells. This therapy involves extracting a patient’s T cells, enhancing them, and reintroducing them to improve cancer fighting capabilities.

A team led by Dr. Maroun Khoury at the IMPACT Center of excellence from the University of Los Andes, in Santiago, Chile, has found that transferring mitochondria—the cell’s energy-producing organelles—from mesenchymal stem cells to T cells can significantly boost their survival rates and cancer-fighting capabilities.

This work was done in collaboration with Dr. Martín Bonamino’s team from the National Cancer Institute (INCA), Rio de Janeiro, Brazil

“It’s like transforming a standard sedan into a race car,” says Dr. Khoury. “These ‘Mito-CAR-T’ cells not only gain enhanced survival; they are equipped for peak performance, enabling them to execute a more efficient assault on cancer cells.”

Published in the Journal of Translational Medicine, the study highlights how this innovative mitochondrial transfer technique can enhance both natural and engineered CAR-T cells, paving the way for advancements in cancer immunotherapy.

“We’re essentially teaching old cells new tricks,” explain the authors. “By amplifying their energy production, we’re giving these T cells a better chance to outlast and outperform their cancer opponents.”

This breakthrough addresses a major limitation of CAR-T therapy—the short lifespan of modified T cells in patients. Manipulation during manufacturing can inflict cell exhaustion, reducing their effectiveness. However, with improved survival rates from mitochondrial enhancements, these modified immune cells could lead to longer-lasting and more effective cancer treatments.

The potential applications of this research extend beyond oncology. Dr. Khoury notes, “This technique could also be transformative for other conditions where bolstering immune cell function is vital, potentially opening new treatment avenues for autoimmune diseases and infections.”

It’s quite a remarkable coincidence that the Chilean-Brazilian paper on mitochondrial transfer in T cells was accepted on the same day, August 14, as another significant study from Europe and the U.S..

This research, titled “Intercellular Nanotube-Mediated Mitochondrial Transfer Enhances T Cell Metabolic Fitness and Antitumor Efficacy,” published in Cell, explores similar themes but offers a more comprehensive approach.

The authors show that the transfer of mitochondria through nanotubes from bone marrow stromal cells to T cells enhances cellular metabolism, enabling engineered T cells and tumor-infiltrating lymphocytes to combat exhaustion and improve their effectiveness against tumors.

Both studies highlight the innovative potential of mitochondrial transfer to boost T cell performance, underscoring a growing interest in this area of research.

Provided by
University of Los Andes