On July 6, 2021 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported the publication of pre-clinical research relating to its second-generation immuno-oncology LBP MRx1299 improving the activity of CAR-T (Press release, 4d Pharma, JUL 6, 2021, View Source [SID1234584624]).
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The research, conducted in collaboration with the Philipps-University Marburg, Germany, and Universitätsklinikum Würzburg, Germany, and published in Nature Communications, demonstrates the ability of the bacterium Megasphaera massiliensis or its short chain fatty acid (SCFA) metabolite pentanoate to enhance the anti-tumor activity of cytotoxic T lymphocytes (CTL) and CAR-T therapies in animal models of cancer, resulting in better tumor clearance.
4D pharma identified M. massiliensis MRx1299 using its MicroRx platform and previously showed MRx1299 to have specific histone deacetylase (HDAC) inhibitory activity and be a rare prolific producer of pentanoate. This led to discussions with the lab of Dr. Alexander Visekruna, corresponding author on the recent publication, due to their work investigating the effects of SCFAs on immune cell subsets.
"Our existing clinical oncology programs, such as the study of MRx0518 and Keytruda in refractory patients, have shown the important role our live biotherapeutics have to play in the fight against cancer in combination with immunotherapies. Using the MicroRx platform we have now shown we have the potential to improve the efficacies of cell therapies such as CAR-T," commented Dr. Imke Mulder, Research Director, 4D pharma. "This demonstrates not only the importance of Live Biotherapeutics as a new modality poised to revolutionize the treatment of a wide range of cancers, but also the power of our MicroRx platform to continue making significant discoveries and advances in this field."
"Collectively, these results suggest that low-abundant commensal bacterial species such as M. massiliensis and their selective metabolites such as pentanoate, rather than broadly distributed and abundant commensals, may be used as specific microbial biotherapeutics to enhance anti-tumor immunity and increase the efficacy of CAR-T therapy for treating tumors," commented Dr Alexander Visekruna of the Institute for Medical Microbiology and Hospital Hygiene at Philipps-University Marburg. "Combined therapies including immune checkpoint inhibitors or CAR-T and simultaneous provision of low-abundant bacteria synthesizing specific metabolites as an adjunctive agent may be therapeutically useful."
Luu et al., Nature Communications, ‘Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer’ View Source