Microbiotica, a clinical-stage biopharma company, has unveiled new preclinical data demonstrating the mechanisms by which its oral precision microbiome medicine MB097 enhances immunotherapy response in cancer patients. The findings were presented at the American Association for Cancer Research (AACR) annual meeting held in Chicago, April 25-30.
Novel Immune Activation Mechanisms Identified
The research reveals that MB097's bacterial strains interact with the immune system through multiple pathways to boost anti-tumor immunity. Three of the nine bacterial species within MB097 induce dendritic cells to produce high levels of interleukin-12 (IL-12), which subsequently stimulates cytotoxic T lymphocytes and natural killer cells with potent tumor cell-killing activity.
Dr. Mat Robinson, Microbiotica's Senior Vice-President of Research, presented the findings in a poster titled "Clinical response to immune checkpoint inhibitors in melanoma is associated with distinct gut bacterial species that promote anti-tumour immunity by different mechanisms."
"These exciting results start to unravel the complex biology of how gut commensal bacteria drive immune checkpoint inhibitor responses," said Robinson. "The induction of dendritic cells to produce IL-12 complement the recently reported data showing that other MB097 strains release metabolites that enhance immune-mediated cancer cell killing."
Multi-Modal Approach to Immune Enhancement
The data demonstrates that MB097's bacterial strains operate through diverse mechanisms beyond IL-12 induction. Certain strains produce metabolites that enhance the tumor cell-killing potential of cytotoxic T lymphocytes, while one strain releases metabolites that reverse the inhibitory effects of tumor-associated macrophages.
Microbiotica developed specialized in vitro human systems using primary immune cells to investigate how gut bacteria modulate the immune response to cancer. These assays provided the foundation for understanding the complex interactions between the microbiome and cancer immunotherapy.
Clinical Development Progress
MB097 comprises nine different species of gut commensal bacteria, all linked to positive checkpoint inhibitor response in multiple clinical studies. The oral live biotherapeutic product is currently being evaluated in an international Phase 1b clinical study as a co-therapy with KEYTRUDA (pembrolizumab) for patients with cutaneous melanoma who have failed to respond to immunotherapies.
The composition of a patient's intestinal microbiome is known to impact response to immunotherapies, particularly checkpoint inhibitors, though the underlying mechanisms have been poorly understood until now. Data readout from the ongoing clinical trial is expected by the end of 2025.
Advancing Microbiome-Based Therapeutics
The research findings demonstrate that different strains within MB097 can interact with the immune system of cancer patients in multiple ways to enhance immunotherapy efficacy. This multi-mechanistic approach represents a significant advancement in understanding how precision microbiome medicines can be developed to improve patient outcomes.
Microbiotica continues to advance its pipeline of live biotherapeutic products aimed at harnessing the power of the human microbiome to improve patient outcomes across various diseases. The company's approach focuses on developing oral precision microbiome medicines that can be used as co-therapies with existing cancer treatments.
