John Gordon: Successful CAR Tcell Therapy – “It’s a Bug’s Life”
John Gordon, Co-Founder, Director and VP of Scientific Affairs at Celentyx, posted on LinkedIn about recent paper by Rishika Prasad and colleagues, titled “Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy” published on Blood.
Authors: Rishika Prasad, Abdur Rehman, Lubna Rehman, Faezeh Darbaniyan, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Eli Zamir, Sabine Schmidt, Tomo Hayase, Chia-Chi Chang, Lauren McDaniel, Ivonne Flores, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E. Fayad, Sairah Ahmed, Swaminathan P. Iyer, Michael Wang, Preetesh Jain, Loretta J. Nastoupil, Jason Westin, Reetakshi Arora, Joel Turner, Fareed Khawaja, Ranran Wu, Jennifer B. Dennison, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Marco L. Davila, Peter Dreger, Felix Korell, Anita Schmitt, Mark R. Tanner, Richard E. Champlin, Christopher R. Flowers, Elizabeth J. Shpall, Samir Hanash, Sattva S. Neelapu, Michael Schmitt, Marion Subklewe, Johannes Francois-Fahrmann, C. K. Stein-Thoeringer, Eran Elinav, Michael D. Jain, Eiko Hayase, Robert R. Jenq, Neeraj Y. Saini
“Successful CAR Tcell Therapy: ‘It’s a Bug’s Life’ Neeraj Saini and Co. show that broad-spectrum Antibiotics Use blunts Therapeutic efficacy due to Loss of Gut Microbiota producing CAR Tcell-boosting Metabolites.
Associations between exposure to broad spectrum antibiotics and inferior outcomes from chimeric antigen receptor (CAR) T-cell therapy are emerging. In a large international cohort of patients with lymphoma who received anti-CD19 CAR T-cell therapy, Rishika Prasad and colleagues found that survival was reduced in patients receiving commonly prescribed extended spectrum antibiotics and that this was associated with dysbiosis of the gut and altered circulating microbial metabolites. In mechanistic murine studies, antibiotics depleted metabolically active commensals whose metabolites were essential for enhancing CAR T-cell efficacy, collectively arguing for increased caution when selecting antibiotics for use prior to CAR T-cell therapy.”
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