Gut microbiome changes improve outcomes in kidney cancer

Gut microbiome

In a Phase I trial, patients with metastatic kidney cancer who took a live biotherapeutic product alongside immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes.

City of Hope, US, researchers are now in discussions with the global SWOG Cancer Research Network to design a Phase II/III trial to assess the novel use of CBM588 and microbiome modulation in people with advanced cancer.

“CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways,” said Sumanta Pal, Professor and Vice Chair of Academic Affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research.

“If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors.”

Microbiome-based interventions in cancer treatment

In the trial, 30 people with metastatic kidney cancer were randomised to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment.

Participants’ gut microbiome were analysed via stool samples in the beginning for a baseline and then again 13 weeks into treatment.

The researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies.

Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator.

“While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies,” said Hedyeh Ebrahimi, City of Hope postdoctoral medical oncology fellow and first author of the study.

City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma.

Scientists from Osel and Miyarisan Pharmaceutical, the manufacturer of CBM588, collaborated on the study.

City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR-T cell therapy. Its enhanced microbiome programme spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery.

Diana Spencer, Senior Digital Content Editor, DDW

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