Scientists have reported new discoveries into the way that CAR‑T cell therapy tackle lymphoma using cutting edge imaging techniques in live mice.
CAR‑T cell therapy involves genetically engineered immune cells, and is approved for use in adults with diffuse large B-cell lymphoma, and other conditions. However, some aspects of exactly how CAR‑T cell therapy works are unknown; for example it was unclear whether they kill cells directly or by inducing other immune cells to attack the tumour.
So Dr Philippe Bousso and colleagues at the Institut Pasteur in Paris, France, carried out a series of tests with mice, using intra-vital imaging to observe how CAR‑T cells attack lymphoma cells in the animals’ bone marrow.
They showed that that tumour cell death was largely due to the engineered cells killing the lymphoma cells directly - as it killed tumour cells within 25 minutes. However, there was a great diversity in the fates of the CAR‑T cells.
Publishing their work in the Journal of Experimental Medicine last week, the authors report that “CAR-T cells represent a potentially curative strategy for B cell malignancies. However, the outcome and dynamics of CAR-T cell interactions in distinct anatomical sites are poorly understood.
“Our results identify a previously unappreciated level of diversity in the outcomes of CAR-T cell interactions in vivo, with important clinical implications.”
Many of the CAR‑T cells attached to normal B cells and lymphoma cells circulating in the blood, which reduced the engraftment of the CAR‑T cells into the bone marrow and so reduced the effectiveness of the treatment. Dr Bousso and the team therefore believe that “purging both circulating tumour and normal B cells prior to CAR-T cell transfer may offer a clinical benefit by improving CAR-T cell engraftment and persistence.”
They conclude: “Understanding these differences [in behaviours] is an important step towards developing strategies to optimise CAR-T cell-based treatments.”
Cazaux, M., Grandjean, C.L., Lemaître, F., Garcia, Z., Beck, R.J., Milo, I., Postat, J., Beltman, J.B., Cheadle, E.J., Bousso, P. (2019) “Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity”, Journal of Experimental Medicine, available at doi: 10.1084/jem.20182375