Identification and analysis of microplastic aggregation in CAR-T cells

Area of Science:

• Immunology
• Environmental Science
• Biotechnology

Background:

• Microplastics (MPs) are emerging environmental contaminants with potential adverse effects on mammalian immune systems.
• Chimeric antigen receptor T cell (CAR-T) therapy is a promising cancer treatment, but its efficacy may be compromised by environmental factors.
• The presence of MPs in CAR-T cell products was observed for the first time, necessitating an investigation into their impact.

Purpose of the Study:

• To investigate the effects of microplastics (MPs) on the functionality of CD19 and BCMA-CAR-T cells.
• To determine the mechanisms by which MPs affect CAR-T cell activity, including apoptosis, ferroptosis, and exhaustion.
• To explore potential therapeutic strategies to mitigate MP-induced impairment of CAR-T cell function.

Main Methods:

• In vitro and in vivo experiments were conducted using CD19 and BCMA-CAR-T cells.
• Flow cytometry, ELISA, and cytotoxicity assays were employed to assess CAR-T cell activity.
• Analysis of apoptosis, ferroptosis, T-cell exhaustion markers, and mTOR signaling pathway activation was performed.

Main Results:

• Microplastics (MPs) were found to suppress the activity of CAR-T cells.
• Exposure to MPs significantly increased apoptosis, ferroptosis, and exhaustion levels in CAR-T cells.
• MP exposure led to hyperactivation of the mTOR signaling pathway in CAR-T cells.

Conclusions:

• Microplastics (MPs) pose a significant threat to CAR-T cell function, impairing their anti-cancer efficacy.
• MPs induce CAR-T cell apoptosis, ferroptosis, and exhaustion via hyperactivation of mTOR signaling.
• Inhibiting the mTOR pathway partially restored CAR-T cell function in the presence of MPs, suggesting a potential therapeutic target.