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

The takeaway

At non-toxic doses, CBD suppressed CD19-CAR T cell proliferation by inducing apoptosis but did not alter their ability to kill cancer cells or secrete cytokines, raising questions about concurrent CBD use during immunotherapy.

People interested in CBD use during cancer treatment, particularly immunotherapy.

CBD preserved CAR T cell killing ability despite reducing proliferation

What the researchers found

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.

Why it matters

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.

The numbers in context

IC50 of CBD: 16-22 microM across NALM6, Raji, and T cells. Maximum non-toxic dose: 8 microM. CBD increased Sub-G1 phase cells (apoptosis marker). No change in antitumor activity or cytokine secretion.

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Preliminary in vitro study using a single CAR T construct. Provides first evidence of CBD-CAR T interaction but requires in vivo and clinical validation.

When this study was published

Published in 2024 in Cannabis and Cannabinoid Research.

The bigger picture

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.

Questions still open

Does reduced CAR T cell proliferation from CBD affect long-term persistence and disease control in patients? Are the CBD concentrations tested achievable in human blood during typical supplementation? Would CBD interact differently with other CAR T constructs?

Common questions

Can CBD interfere with CAR T cell therapy?

This lab study found CBD reduced CAR T cell proliferation but did not impair their ability to kill cancer cells. Whether this reduced proliferation matters clinically remains unknown and needs further study.

Should cancer patients avoid CBD during immunotherapy?

This study raises a flag but does not provide a definitive answer. CBD reduced immune cell growth without affecting killing function. Patients should discuss supplement use with their oncology team.

Read the original research

Effects of Cannabidiol on the Functions of Chimeric Antigen Receptor T Cells in Hematologic Malignancies.

Cannabis and cannabinoid research, 9(3), 819-829

View on PubMed ↗Publisher’s paper ↗

Citation

Chantarat, Natthida; Pe, Kristine Cate S; Suppipat, Koramit; Vimolmangkang, Sornkanok; Tawinwung, Supannikar. (2024). Effects of Cannabidiol on the Functions of Chimeric Antigen Receptor T Cells in Hematologic Malignancies.. Cannabis and cannabinoid research, 9(3), 819-829. https://doi.org/10.1089/can.2023.0108