CAR-T Meeting 2025 | Utilizing mitochondrial transfer for adoptive T-cell therapy

So mitochondrial transfer is a phenomenon that was described almost 10 years ago, but it’s still relatively unappreciated. So what we did in our study, we developed a co-culture system in which we expose T-cells, that can be either CAR T-cells, TCR-engineered T-cells, or even TILs, with bone marrow-derived stromal cells. 

What we saw is that the two cell types form intercellular tunneling nanotube connections and this enables the trafficking of mitochondria from the bone marrow stromal cells to CD8 T-cells and this results in better metabolic fitness of the recipient cells, the CD8 cells. 

When we use these cells supercharged with extra mitochondria, these cells are able to induce more profound and robust and long-lasting anti-tumor responses in vivo across a different model in syngeneic animal model, tumor animal model like B16 melanoma. We did this with CAR T-cell therapy using NALM6 leukemia. And what we observed was essentially that the extra mitochondria enabled the cells to proliferate better, persist better. They also were able to infiltrate more deeply into the tumor tissue compared to cells that didn’t receive mitochondria. And also the extra mitochondria enabled cells to acquire a program of resistance from T-cell exhaustion. So they were less exhausted with more effector and cytotoxic function. So I think that this is an exciting new technology that is emerging that can tackle many of the issues of T-cell therapy because it can result in better outcomes for different problems that are in the field.

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