Visualizing T Cells Fight Cancer in Real Time

When cancer escapes the immune system, our defenses are rendered powerless and are unable to fight against the disease. Chimeric antigen receptor T (CAR T) cells represent a promising immunotherapy strategy, developed with the aim of tackling tumors head on. But the occurrence of relapse in some patients remains a challenge. In research published last week in JEM, scientists identified the precise function of CAR T cells in a bid to optimize future therapies.

“By identifying the strengths and weaknesses of CAR T cells in action, this research opens up new avenues for exploiting and optimizing the activity of CAR T cells in patients,” says senior author Philippe Bousso of the Institut Pasteur.

One of the current strategies used to combat cancer is based on modification of the patient’s natural killer cells to make them recognize the target molecule CD19 expressed by the tumor so that they can eliminate it. Clinical trials have proved to be remarkably effective, leading to the use of this technique in adults and children to treat blood cancer, but some patients suffer relapses.

Using a novel high-resolution in vivo imaging technique, the team visualized CAR T cells battling a tumor for the very first time. This enabled them to investigate the overall behavior of CAR T cells and to visualize in real time the interactions between CAR T cells and the tumor as well as tumor death. Even if some CAR T cells are more active than others, the team demonstrated that, in general, a CAR T cell is capable of directly killing a tumor cell within approximately 25 minutes of recognizing its target.

“Mathematical simulations based on our experimental data confirm that the efficacy of CAR T cells is primarily based on their ability to engage and directly kill the cancer cell rather than recruiting other immune cells to the tumor site,” Bousso explains.

These simulations also demonstrated that the number of CAR T cells that are able to infiltrate the bone marrow plays a major role in treatment efficacy. A significant obstacle for this infiltration is that CAR T cells in the bloodstream encounter tumor cells and B lymphocytes that also express the target CD19. Reducing the number of cells expressing CD19 before the injection of CAR T cells significantly improved the overall survival of the mice.