Microbiome modulation to unlock immunotherapy
Changing the gut bacteria of a patient whose immunotherapy stopped working, in the hope of restarting the response.
Gut composition predicts checkpoint-inhibitor response across cohorts, and small single-arm studies of faecal transplant from responders reported that a minority of refractory melanoma patients regained response. Randomised work is now running: LND101 with checkpoint blockade in advanced melanoma (NCT06623461, phase 2, Canadian Cancer Trials Group), an Oslo phase 2 using responder stool (NCT05286294), and a Netherlands Cancer Institute study (NCT05251389). Defined bacterial consortia are being developed as an alternative to whole stool.
How it works
Transferring or supplementing gut commensals alters antigen presentation, systemic interferon tone, and intratumoural T-cell infiltration, restoring sensitivity to PD-1 blockade.
- Cheap and repeatable
- Targets the host, so it is tumour-genotype agnostic
- Randomised trials now running
- Donor variability and transmission risk with whole stool
- Effect sizes uncertain; no phase 3
- Antibiotics and diet confound everything
Latest papers
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