Past research has long suggested the significant impact of the microbiome on the efficacy of various anticancer treatments, including chemotherapy, CAR T-cell therapy, targeted therapies, and radiation therapy. Emerging research further highlights the critical role of the intestinal microbiome in influencing the outcomes of CAR T-cell therapy by possibly enhancing its efficacy while reducing toxicity.
Dr. Melody Smith, MD, MS, a medical oncologist and hematologist at Stanford Medicine, presented her findings at the recent AACR Immunotherapy Conference. Her studies, conducted at Memorial Sloan Kettering and the University of Pennsylvania, reveal compelling insights into how microbiome composition and prior antibiotic use affect treatment efficacy and toxicity.
CAR T-cell therapy, while revolutionary, can cause several side effects. These include:
Immune effector cell-associated neurotoxicity syndrome (ICANS): A severe side effect characterized by neurological symptoms such as confusion, seizures, or coma, often linked to antibiotic exposure prior to therapy.
Cytokine release syndrome (CRS): A common side effect involving a systemic inflammatory response. Interestingly, no significant link was found between antibiotic exposure and CRS in Dr. Smith’s research.
B-cell aplasia: The absence of normal B cells, leading to weakened immunity.
Cytopenia: A reduction in blood cell counts, which increases the risk of infections.
Cardiotoxicity: Although rare, CAR T-cell therapy can have adverse effects on the heart.
Dr. Smith’s research found that certain antibiotics, particularly those targeting obligate anaerobes (e.g., piperacillin, tazobactam, imipenem, and meropenem), negatively impact CAR T-cell therapy outcomes. Patients exposed to these antibiotics in the four weeks prior to therapy exhibited reduced overall survival and progression-free survival. This highlights how microbiome disruptions, or dysbiosis, can hinder CAR T-cell responses.
Interestingly, these patients were also more prone to developing ICANS. However, no significant link was observed between antibiotic exposure and CRS.
Dr. Smith suggested that dietary interventions in optimizing microbiome health may improve CAR T-cell therapy outcomes. Diets rich in fiber and fermented foods are known to promote microbiome diversity. While no concrete data exist for CAR T-cell therapy yet, insights from other cancer immunotherapy studies suggest that diet could play a pivotal role.
Chemotherapy Impact on the Microbiome
Chemotherapy and conditioning regimens, which often precede CAR T-cell therapy, are also known to alter the microbiome. However, the precise effects of these changes on CAR T-cell functionality remain an area for further investigation. Dr. Smith’s ongoing studies aim to unravel how these alterations influence therapy outcomes and whether targeted interventions can mitigate negative impacts.
The Future of Microbiome Research in CAR T-Cell Therapy
Dr. Smith’s research opens new avenues for improving CAR T-cell therapy outcomes by focusing on the microbiome. Future studies may validate the role of dietary and other microbiome-modifying interventions, potentially transforming the pre-treatment protocols for patients.
With ongoing advancements in both CAR T-cell therapy and microbiome research, the potential to enhance treatment efficacy while minimizing toxicities holds great promise for patients battling hematologic malignancies.
Created: Feb 24th, 2025
Citations:
Hippensteele, A., & Smith, M. (2025, February 21). Intestinal microbiome may play a role in CAR T-cell therapy outcomes. Pharmacy Times.
Hippensteele, A., & Smith, M. (2025, February 22). Harnessing the microbiome may help reduce CAR T-cell therapy toxicity. Pharmacy Times.
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