“We can now conclude that CAR-T cells can actually cure patients” – Carl June, pioneering CAR-T scientist.

Excerpts from the Endpoints article:

“A decade after the first-ever patients were infused with CAR-T, at least two of them remain cancer free and their genetically modified cells still appear active, surveilling their blood for any budding malignancies that dare crop up.

“We can now conclude that CAR-T cells can actually cure patients, based on these results,” Carl June, the University of Pennsylvania immunologist who designed the first treatment, told reporters Wednesday, adding the results came as a surprise. “We did not think that this would be a curative therapy at all in 2010.”

Over the last 10 years, June and a fellow Penn immunologist, Joseph Melenhorst, have regularly sampled blood from the first patients in the 2011 trial. At the time, the notion that you could treat cancer patients by removing their immune cells, strapping on tumor-seeking missiles and then reinfusing them, was the dream of a handful of researchers and wealthy financiers.

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With their samples, June and Melenhorst have been able to track how the T cells change in the early patients, offering basic biological insights that might help researchers design new treatments in the future. Although these two patients in the study are still cancer free and five different CAR-T therapies are FDA-approved, the majority of leukemia patients who receive CAR-T are not cured and researchers have long struggled to show any efficacy in solid tumors.

The pair’s new paper, published Thursday in Nature, shows that CAR-T cells are still active a decade after treatment, in far lower but still measurable numbers. By culturing the extracted CAR-Ts alongside cancer cells in a dish, they showed that the cells retain their serial-killing capacity, as June has often described it.

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“These are things we’ve hypothesized to be doable with CAR-T,” said Yvonne Chen, an immunologist at UCLA who was not involved in the work. “Now we know that it can happen.”

The two patients had chronic lymphocytic leukemia, a disease that, as its name implies, is generally considered incurable. The new findings suggest that for other incurable leukemias — such as follicular lymphoma and multiple myeloma — researchers may want to engineer CAR-Ts to have maximal persistence, said Frederick Locke, an oncologist at Moffitt Cancer Center.

“I think the answer is, yeah, you can use this data to try to inform CAR manufacturing and CAR design,” Locke said.