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Final Program


Final Program

Immuno-engineering and Cellular Therapies

"Gut microbiota and metabolites influence CAR-T Cell persistence, efficacy and predict outcomes in multiple myeloma"

W104 - Gut Microbiota and Metabolites Influence CAR-T Cell Persistence, Efficacy and Predict Outcomes in Multiple Myeloma

Wednesday, June 25, 2025
7:30am - 7:30pm East Coast USA Time
Abstract Text: Multiple myeloma is a hematologic malignancy that remains incurable despite advances in immunotherapies like CAR-T cell therapy. This study investigates the role of gut microbiota in clinical outcomes for multiple myeloma patients treated with the humanized BCMA-directed CAR-T therapy, ARI0002h. Gut microbial metabolites, particularly succinate, were associated with CAR-T cell phenotypes and persistence. In CAR-T cell cultures, higher succinate levels correlated positively with CD4+ central memory cells, enhancing respiratory capacity. In a murine myeloma model, a diet increasing intestinal succinate levels improved CAR-T cell persistence and tumor control. Furthermore, specific bacterial taxa like Acidaminococcaceae, Monoglobaceae, or Akkermansiaceae and metabolites like tyrosine associated with CAR-T cell clinical outcomes. These microbial profiles were integrated into predictive response models that identified patients likely to achieve a complete response by day 100 and 180 post-infusion. Additionally, a response improvement model effectively identified patients likely to improve their response from a partial to a complete response by day 100 post-infusion These findings suggest that gut microbiota correlates with CAR-T cell therapy efficacy and can be a valuable tool for risk prediction.