How to make CAR-T therapy safer?

In the dark laboratory, a rat with a shaved backside is lying on the operating table

The magical scene appeared in the biology laboratory of Texas A&M University (Texas A&M University)

CAR-T cell therapy has been a hot field of cancer treatment in recent years, and a number of therapies have been approved for the treatment of blood cancer

Second, CAR-T cells are extremely active, and their attack response is "explosive", and the large-scale inflammatory response caused will bring unnecessary toxic side effects

Because it is very difficult to find a "perfect" antigen target that is only expressed on the surface of tumor cells, scientists have turned their attention to other methods to increase the specificity of CAR-T therapy

One way is to divide the chimeric antigen receptor (CAR) of CAR-T cells into two pieces, and insert a light switch-a protein called LOV2, into the circuit where it works

▲The mechanism of action of LiCAR-T cell therapy (picture source: reference [1])

So how can external light activate CAR-T cells in the body? The research team worked with bioengineers at the University of Massachusetts Medical School (UMass Medical School) to design an injectable nanoparticle that emits blue light when exposed to near-infrared light

In mouse tumor model experiments, this CAR-T cell only kills tumors exposed to light, but has no effect on other tumors in the animal body, showing a very high specificity

▲LiCAR-T cells shrink tumors with a high degree of specificity (picture source: reference [1])

Moreover, compared with conventional CAR-T therapy, the toxic and side effects of LiCAR-T cells are much smaller.

▲Mice receiving conventional CAR-T therapy have continued to lose weight during the treatment, while mice receiving LiCAR-T therapy have maintained their normal weight (picture source: reference [1])

Although the potential of this research is exciting, it still has certain limitations

In any case, LiCAR-T cells have ignited a promising light on the way to explore the limitations of CAR-T cell therapy

Reference materials:

[1] Nguyen, NT, et, al.

[2] In research on mice, scientists use light to paint a more precise target for CAR-T to attack tumors.