CAR T-cell therapy has been preventing leukemia in patients from going into remission for more than 10 years

49-year-old Doug Olson had a wife and four children when he was diagnosed with chronic lymphocytic leukemia in 1996. His initial treatments were quite successful, but by 2010, nearly 50% of his bone marrow he got cancer.

That’s when he enrolled in a clinical trial of a new cancer therapy led by his oncologist, David Porter from the University of Pennsylvania’s Perelman Center for Advanced Medicine, along with another patient. Experimental treatments, also known as CAR T-cell therapywill tune Olson’s own immune cells to detect and destroy leukemia cells, and bring them back into his body through a blood transfusion – something that had previously only shown promise in the trials above. mouse.

Olson started to feel the results after just a few weeks. “That’s when Dr. Porter walked into my ward and he hotly announced to the press that 18 percent of my white blood cells were CAR T cells,” Olson said at Tuesday’s press conference. “I’ll tell you that moment, I was absolutely convinced that this thing was working and I was going to be fine.”

The following week, Porter told Olson that clinicians could not find a single cancerous cell in his body.

Now, more than 10 years later, Olson is still cancer-free.

In a peer-reviewed study published todayin the magazine nature, Porter and the doctors followed Olson’s journey documenting the experimental treatment and its results. The findings show that even after ten years, Olson and another patient are still cancer-free thanks to CAR T-cell therapy – confirming its amazing effectiveness and opening the door for its use in more cases of leukemia and other cancers in the future.

“It’s an exciting new therapy, but we’ve all been involved in many, many, many different new therapies and it’s rare to come across something that has such a dramatic effect. “. Porter, the lead author of the new paper. “The responses have been beyond our expectations, definitely mine.”

T cells are an essential component of the immune system. They can both direct other immune cells to attack invading pathogens and destroy pathogens themselves. T cells live for a very long time and can form lifelong memories of what they have previously recognized, such as when exposed to a childhood virus.

In CAR T-cell therapy for cancer, the patient’s own T cells are collected and genetically engineered to produce a molecule known as Chimeric Antigen Receptor, or CAR. These CARs allow T cells to identify cancer cells with a laser focused on the eye and remove them. Millions of millions of CAR T cells are created in the laboratory, then reintroduced into the patient’s body through a blood transfusion. In theory, CAR T cells could infiltrate and eliminate tumor cells with extreme speed and precision. And because they retain such good memories and can circulate in the body for a long time, they should be able to prevent the same cancer from coming back.

But Porter and his colleagues were amazed to see that the therapy suppressed cancer cell resurgence for such a long time in this latest study, due to the high rate of leukemia remission. They suspect CAR T cells evolve in patients over time to learn better ways to hunt down tumor cells.

“[CAR T-cells are] wear many hats,” Joseph Melenhorst, an UPenn immunologist and co-author of the new paper, told reporters Tuesday. “You know, we call these cells a living therapy. The main finding in this paper is that 10 years later, you can find them, but they’ve evolved. “

The researchers don’t know if there were still white blood cells that formed in Olson’s body and were simply being rapidly killed by CAR T cells while on patrol; or whether there has really been no cancer activity in the patient since 2010. What they do know, however, is when Olson’s CAR T cells were taken out of his body and faced with leukemia. in the lab, they can still kill.

Since that clinical trial in 2010, CAR T-cell therapy has now been approved by the FDA for six different indications, and acute leukemia is routinely treated with this therapy worldwide. But these are the first results to determine how long it might work for the tens of thousands of people who have already received the treatment.

The big barrier for patients, unfortunately, is price. CAR T-cell therapy can cost between $300,000 and $500,000. Researchers are trying to create less expensive over-the-counter therapies that take a similar approach, with cells generated from other donors in bulk.

Later, it is hoped to be able to expand the therapy to treat solid cancers, such as breast, lung or pancreatic cancer. Tests are currently underwaybut the results so far have not been particularly encouraging.

And although the two cases explored in the new paper have shown very promising results, the long-term effects of CAR T-cell therapy still need to be studied more extensively. Some patients report worse side effects because CAR T cells have some distinct toxicity. Even Olson’s positive results are affected by tumor lysis syndrome, where the rapid destruction of cancer cells leads to an adverse immune response and causes flu-like symptoms. vomiting, nausea and joint pain.

And there are some cases where CAR T cells have lost some of their effectiveness, especially in trials against solid tumours.

“The biology of long-lived CAR T cells is still not fully understood,” Sara Ghorashian, a CAR T cell researcher from University College London who was not involved in the study, told The Daily Beast. It’s still not entirely clear why some patients will find CAR T cells persist for years, while others may experience a decrease in effectiveness in less than six months.

A wide range of unknown factors can be present and Ghorashian cautions against extrapolating the findings to all CAR T therapeutic bases.

However, within a decade, CAR T cells have exploded as a game-changing form of cancer treatment. And findings like those of Porter and his colleagues will only spur more efforts to learn more about how this therapy works and how we can help the many patients who are fighting for life. their access to it.