Boosting the CAR T party.

This week’s Cool Cancer Find takes us again to the world of cancer immunotherapy via a type of treatment called CAR T cell therapy. To better understand the impact of this incredible paper and CAR T, think about your immune system like this: if you were building an elite team of superhero soldiers to defend a city from a powerful enemy, you would want these superheroes to be strong, smart, and durable enough to keep fighting, even when the going gets tough. This is what cancer researchers do with CAR T cell therapy.

?

During CAR T therapy, our body's own superhero soldiers (called T cells), are given special training (genetic modifications), and then sent back into the city (our body) to hunt down the bad guys (cancer cells). The problem is, after some time, even superheroes can get tired, or "exhausted," and lose their superpowers. When that happens, the enemy (cancer cells) can start causing trouble again.

Researchers including the V Foundation grantee Dr. Evan Weber Children's Hospital of Philadelphia have been looking (HARD!) for a way to keep our superhero soldiers, the CAR T cells, strong and full of energy, so they can fight cancers longer and better.

?

In a VERY, VERY cool study, Dr. Weber and team found a special key that might help. This key is was a discovery involving the protein FOXO1, which works like an energy boost (just like the way a sugar free Monster works for me ??) for CAR T cells. FOXO1 helps CAR T cells stay sharp, remember their anti-cancer training, and keep fighting.

Think of FOXO1 as a superpower battery charger for our superhero CAR T cells. When CAR T cells have plenty of FOXO1, they can stay energized and active, allowing them to fight cancer for a longer time. On the other hand, if they don't have enough FOXO1, they start to lose their strength and memory of how to battle the enemy.

In this study, Dr. Weber discovered that by increasing the levels of FOXO1, the CAR T cells became more resilient and effective. The Weber team also found that other similar proteins to FOXO1 didn't have the same effect, showing that FOXO1’s role is unique role in keeping these T cells at their best.

?

The exciting part from this work to me is that the field can now focus on FOXO1 as a key protein in cancer immunotherapy, enabling the creation of CAR T cell therapies that last longer and work better against cancer. This fundamental advance could mean fewer relapses and better outcomes for patients. It's like finding a way to give these superhero soldiers endless energy, so they can keep protecting the city from those tricky enemy. Fight on Dr. Weber, fight on.

Learn more about the work that Dr. Weber and his lab are doing here Our Team — Weber Lab (theweberlab.org) and read his recent publication by following the link from Nature Portfolio https://www.nature.com/articles/s41586-024-07300-8

?