A pioneering CAR-T cell therapy study from Novartis and the University of Pennsylvaniademonstrates the impressive potential of the next-generation therapy. Five years after the start of the study, three patients have achieved complete remission and remain cancer-free.

Here it is, the proof that the hype about CAR-T cell therapy was no hollow promise.

Penn’s Abramson Cancer Center and the Perelman School of Medicine developed a CAR-T cell therapy approach called CTL019. It is a patient-specific treatment, in which the T-cells – or the natural serial killer of the immune system – are isolated from the individual and modified with chimeric antigen receptors (CAR’s). These target the CD19 protein on the cancerous B cells in leukemia, helping the immune system to again recognize the cancer . The ‘armed’ T-cells are then given back to the patient.

Interim results of the study were already published in 2011. Back then, three patients with chronic lymphocytic leukemia (CLL) received the therapy. Two of them remained in remission more than a year after the treatment – a breakthrough for the T-cell engineers, and reason enough for Novartis to step in and enable further advancement.

Up until today, 14 patients have received the therapy and their progress was published in Science Translational Medicine. So, let’s begin with the impressive part: Four patients (29%) achieved a complete remission. One of them died in remission after 21 months due to an infection after a surgery. The other three however, show no evidence of cancer so far, nor are they dependent on other treatments. What is even more impressive is that one of these patients received the therapy more than five years ago.

Carl H June_car-t_novartis

“Importantly, our tests of patients who experienced complete remission showed that the modified cells remain in patients bodies for years after their infusions, with no sign of cancerous or normal B cells,” said the study’s senior author, Carl H. June. “This suggests that at least some of the CTL019 cells retain their ability to hunt for cancerous cells for long periods of time.”

However, not all of the patients benefited from the therapy like this. Four patients achieved partial response with therapy effects lasting a median of seven months. Two died after 10 and 27 months due to cancer progression. One progressed after 13 months, but remained alive on other therapies for 3 years.

Six patients didn’t respond to the therapy, which was attributed to the fact that the modified T-cells did not expand as strongly in these patients. Two of them died, whilst the remaining four are receiving other therapies.

To summarise: Only 30% of the patients responded well to the therapy,  so how could the other 70% be treated?

Personalized studies are only useful when we know why a therapy is working in one person and not in another. More data is needed to adjust the therapy to age, prior treatments or certain biomarkers (read our analysis of the future of biomarkers in immuno-oncology). The team further plans to test combinations of CTL019 with immune checkpoint inhibitor drugs or other therapies to stimulate T-cell recognition of tumor cells.

Another approach is currently explored by the miraculous French biotech Cellectis, which develops “off-the-shelf”- products (i.e. engineered T-Cells from a healthy donor). This approach could be even more promising, as it skips the laborious task of customizing the T-cells to each patient individually.

Whatever strategy wins the race, the study strikingly highlights the long-term effects of CAR-T therapy. Just wondering: If the treatment doesn’t have to stop to protect the body from a relapse, could it be considered as the ultimate cure for cancer?


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