Driving next-generation CAR-T therapy

A little over a decade ago, a then-six-year-old patient named Emily Whitehead underwent an experimental treatment for late-stage blood cancer – CAR-T cell therapy. Doctors extracted immune cells called T cells from her blood, and in a lab, genetically reprogrammed them to become cancer-hunting CAR-T cells. These cells were then returned to Emily’s body. Within a few weeks her cancer was in full remission. In the spring of 2022, she celebrated 10 years “cancer free.”

Today, CAR-T therapy has changed the paradigm for how patients with certain blood cancers are treated. Inspired by stories like Emily’s, scientists continue to innovate and explore CAR-T therapy. But cancer is incredibly complex, and many challenges still need to be overcome. For example, not all patients respond to treatment with CAR-T therapy, and it’s currently available for only certain types of cancers.

What can we do to improve on the next generation of CAR-T therapies, so that they can potentially help more patients? We build a fresh foundation.

A refined approach

Every CAR-T therapy is custom made for a single patient, using the patient’s own cells. It’s a sophisticated process, requiring many steps to take T cells from a patient to a lab and back to the patient again, safely and reliably.

Making this manufacturing process better and faster – so that we can potentially create more effective and longer-lasting CAR-T cells – is the goal of an investigational next-gen CAR-T platform at Novartis called T-Charge™. How? By preserving a special property associated with younger T cells, called “stemness.”

With stemness, T cells have an increased ability to self-replicate. Next-gen CAR-T cells created through T-Charge retain stemness, giving them the potential to continuously self-renew and mature within a patient’s body. This is important because stemness may lead to fewer “exhausted” T cells and is closely tied with therapeutic potential and durability. The hope is that this can help lead to improved outcomes for patients – and Novartis scientists are diligently investigating its potential in clinical trials.

The need for speed

There’s another potential benefit – with increased stemness, next-gen CAR-T cells primarily replicate and expand within the patient’s body. In this way, the investigational T-Charge platform could help reduce the time T cells need to spend growing in the lab, as well as potentially reducing the overall number of cells that need to be returned to a patient’s body.

By shortening and simplifying the manufacturing process, next-gen CAR-T therapy could potentially be given to patients much faster than currently possible, making the treatment available to more patients who could benefit.

Better and faster are hopefully just the beginning. T-Charge is a technology platform, a foundation on which to build future CAR-T therapies that can address more of the challenges that cancers pose. Like radioligand imaging and therapy, it has potential to be a pillar for cancer care. Next week, we’ll look at one more potential pillar – one that takes out cancer’s trash.