CAR-T Meeting 2025 | Microbiome-derived metabolites to guide patient outcome prediction and CAR T-cell engineering

We have identified a commensal metabolite that is coming from the human microbiome – it’s called pentanoate. And pentanoate has the ability to first serve as a biomarker for the survival of CAR T-cell patients, telling us that the microbiome plays a very important role in how CAR T-cells react in the patient, how they respond. 

We have further investigated the mechanism of how pentanoate acts on CAR T-cells while we are engineering them. And we have seen that it acts first of all as an epigenetic modulator, but also as a metabolic one. As it is metabolized and directly taken up by the TCA cycle, where it ends up in the nucleus again as system modification. And all of that is causing a better phenotype for the T-cells. They become more persistent, they become naive-like, and they are way better in protecting against tumors. 

On one hand, we need to take a look at how we treat patients with antibiotics, because a broad application might not be convincing. If we treat patients with broad-spectrum antibiotics, that might be very harmful for the therapy by itself. However, we need to find ways to either target the microbiome more specifically or use metabolites from the microbiome, they are more precise when we apply them to the patient or to the T-cell product. So we can now influence the way we manufacture T-cells with parts of the microbiome without using it as a whole.

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