24 Dec UPenn Study Finds Evidence Immunotherapy Can Be Influenced by Diet

MedicalResearch.com Interview with:

Dr. Shan Liu

Shan Liu, PhD, Postdoctoral fellow
Perelman School of Medicine
University of Pennsylvania

MedicalResearch.com: What is the background for this study?

Response: Our study provides evidence that the efficacy of CAR T cell immunotherapies can be influenced by an important lifestyle factor: diet.

MedicalResearch.com: What are the main findings?

Response:  Our study found that a ketogenic diet can enhance CAR T cell function through its metabolite, β-Hydroxybutyrate (BHB). Importantly, instead of altering the diet, providing BHB via oral supplementation in our preclinical model is sufficient to improve the anti-tumor function of CAR T cells. However, it’s important to note that we’re still in the early stages, and we’re not yet recommending any dietary changes or supplements for patients.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Our study shows that BHB alone can enhance CAR T cell therapy, similar to the ketogenic diet, and we hypothesize that oral BHB supplementation could improve patient compliance.

The next step is to test the safety and feasibility of administering BHB orally to Non-Hodgkin lymphoma (NHL) patients receiving CART19 immunotherapy, while also assessing the effects of BHB on Peripheral blood mononuclear cells (PBMCs).

Additionally, since the ketogenic diet can influence the gut microbiome, we are interested in exploring the role of gut microbiota in mediating the enhancement of CAR T cell function.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: This work would not have been possible without the invaluable contributions of my co-leader, Dr. Puneeth Guruprasad, PhD, and the constant support from our mentors, Dr. Marco Ruella, MD, and Dr. Maayan Levy, PhD. I would also like to acknowledge all of our collaborators, whose expertise and teamwork were essential in advancing this study. The collaborative environment at Penn has been instrumental in driving this project forward, not only by fostering cross-disciplinary collaboration but also by enabling the critical transition from research to clinical application.

I have no conflicts of interest to report at this time.

Citation:  ASH 2024 abstract:
Shan Liu, Puneeth Guruprasad, Kecheng Han, Luca Paruzzo, Alexander Shestov, Andre Kelly, Kevin R. Amses, Amichay Afriat, Bhoomi Madhu, Lev Litichevskiy, Ezra Dubowitz, Neil Tangal, Alana McSween, Melody Tan, Alberto Carturan, Andrew Lee, Yunlin Zhang, Giulia Gabrielli, Raymone Pajarillo, Ruchi P. Patel, Guido Ghilardi, Patrizia Porazzi, Stephen J. Schuster, Roddy S. O’Connor, Michael C. Milone, Joshua Rabinowitz, Maayan Levy, Marco Ruella; Ketogenic Diet Enhances CAR T Cell Antitumor Function Via β-Hydroxybutyrate. Blood 2024; 144 (Supplement 1): 4. doi: https://doi.org/10.1182/blood-2024-208913

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Last Updated on December 24, 2024 by Marie Benz MD FAAD