CBD reduced CAR T cell proliferation but did not impair their cancer-killing ability

CBD at 8 microM (the maximum non-toxic dose) did not alter CAR T cell surface expression, immune characteristics, T cell subset, or memory phenotype. However, CBD suppressed CAR T cell proliferation by inducing apoptosis (increased Sub-G1 phase). Critically, antitumor activity and cytokine secretion were not affected.

CD19-CAR T cells were generated by retroviral transduction and exposed to CBD. Cell viability (WST-1 assay), surface markers (flow cytometry), proliferation, apoptosis, cell cycle, degranulation, and antitumor activity were assessed. IC50 of CBD was 16-22 microM across cell lines.

Cancer patients increasingly use CBD as a palliative supplement during treatment, including during CAR T cell therapy. This is the first study to directly examine whether CBD interferes with CAR T cell function, finding a nuanced effect: reduced proliferation but preserved killing ability.

CAR T cell therapy is a breakthrough cancer treatment, and CBD is one of the most commonly used supplements among cancer patients. Understanding their interaction is critical for patient safety. The finding that CBD reduces proliferation but not killing suggests a potential clinical concern that warrants further investigation.

In vitro study that does not account for CBD metabolism, bioavailability, or tissue distribution in vivo. The CBD concentrations tested may not reflect what reaches immune cells in patients. Only one CAR T construct (CD19) was tested.