Researchers used two-photon microscopy to demonstrate that chimeric antigen receptor (CAR) T cells can induce tumor regression by directly targeting and killing cancer cells. The study revealed new details about how these immune cells work. It also improved their effectiveness in treating non-lymphoma Hodgkin’s and other B cell cancers.
The researchers monitored the activity of anti-CD19 CAR T cells injected into mice with B cell lymphoma. They observed individual CAR T cells killing lymphoma cells in the animals’ bone marrow using intravital two-photon microscopy. Some CAR T cells appeared to be more active than others, but lymphoma cells died in most cases within minutes of coming into direct contact with a CAR T cell, implying that CAR T cells kill their targets directly.
Computer simulations based on experimental data supported the idea that CAR T cells eliminate the majority of B cell lymphoma in the bone marrow through direct cytotoxic activity rather than by recruiting and activating other cells.
Reducing CAR T cells’ encounters with lymphoma cells enhanced the ability of CAR T cells to kill tumor cells. The two-photon microscopy findings show that CAR T cell behaviors vary significantly across anatomical sites, with implications for engraftment, anti-tumor activity, and tumor relapse.