Chimeric antigen receptor (CAR) T cell therapies have changed the way that many blood cancers are treated. A type of immunotherapy, CAR T cells redirect a patient’s own immune system in the fight against cancer. Memorial Sloan Kettering Cancer Center (MSK) has been a leader in developing CAR T cell treatments for acute lymphoblastic leukemia, B cell lymphomas, multiple myeloma, and other blood cancers.
But for one particularly aggressive blood cancer, acute myeloid leukemia (AML), CAR T cell therapy has not yet been successful. There is a huge unmet need for finding better ways to treat AML that comes back after initial treatments, because current options are extremely limited.
Now researchers are reporting clinical and translational findings from the first-ever clinical trial at MSK to evaluate a novel CAR T cell therapy in patients with advanced AML. The pilot study, which enrolled five patients, was based on scientific discoveries made in labs at MSK. The cells used to treat the patients in the trial also were engineered in MSK facilities.
The trial used a new kind of CAR T cells that were modified to recognize a protein expressed on the surface of AML cells. Additionally, the cells secrete a protein messenger that boosts their own killing capacity while also helping to recruit other immune system players to fight the cancer. The findings were published August 27, 2025, in the journal Blood.
“We’re all excited about the promise and hope that this study gives us for treating AML,” says leukemia specialist Susan De Wolf, MD, a co-first author of the paper. “We are also excited that all of the research that led to this trial came out of MSK.”
What Is CAR T Therapy?
CAR T cell therapy is a treatment approach that uses the body’s own immune system. With this therapy, the patient’s T cells, a type of immune cell, are removed from the body and engineered in the lab to recognize a protein, or marker, present on the cancer cell. When these engineered cells are infused back into the body, they seek out and destroy cancer cells.
“CAR T cell therapy has been effective in treating many types of blood cancer, including B cell leukemias and lymphomas and multiple myeloma,” says leukemia specialist and cellular therapist Mark B. Geyer, MD, who designed the new pilot study. “But it has been challenging to develop a CAR T cell therapy for AML.”
Why Is AML So Hard To Treat?
AML is an aggressive blood cancer that grows rapidly and is hard to eliminate completely from the body. The most effective therapy for patients with higher-risk AML is a stem cell or bone marrow transplant. If the cancer comes back after the transplant, patients often have few good treatment options available.
Dr. Geyer explains that one reason AML is difficult to treat with CAR T cell therapy is because AML cells tend to be heterogeneous, meaning they don’t all have the same markers. Therefore, it’s harder to eliminate all of the cancer cells with the same type of CAR T cell. Additionally, some of the markers found on AML cells are also found on normal blood stem cells. These stem cells are needed for the body to grow new, healthy blood cells. So it’s important to protect them, rather than attack them.
What Makes These CAR T Cells Effective Against AML?
Work on these CAR T cells began in the lab several years ago, with the aim of developing a product capable of rapidly overcoming any immune suppression that AML cells could put up. To accomplish that, these CAR T cells were engineered to specifically target CD371 (a marker present on most leukemia cells in most AML patients), to be driven by a powerful internal engine called SAVVY, and to secrete a biologic fuel called interleukin (IL)-18.
This approach was developed by leukemia specialist and cellular therapist Anthony Daniyan, MD, a researcher in MSK’s Cellular Therapeutics Center and the senior author of the Blood paper.
“The goal of my research for many years has been to find new ways to make CAR T cells as potent as possible,” Dr. Daniyan says. “Adding IL-18 not only makes the T cells more active, but it also recruits other immune cells to help fight the cancer. This is especially important because not every AML cell has CD371 on its surface.”
One of the other types of immune cells that the new CAR T cells may recruit are called natural killer (NK) cells. Their increased presence and activated cell state in patients who respond to the CAR T cell infusion likely boosts the CAR T cells’ effectiveness, Dr. Daniyan adds.
“NK cells have a very activated and cytotoxic profile during the time that CAR T cells expand in patients, which suggests that they may have the capacity to kill cancer cells,” says study co-first author and cellular therapist Xiaoli Mi, MD. “The patients who responded to the treatment had a lot more NK cells than the nonresponders.”
New CAR T Cells Are Powerful, so Fewer Are Needed for Treatment
Another benefit of the dual-engineering approach is that these cells tend to be much more powerful than other types of CAR T cells, which means that far fewer cells are needed to treat patients.
“This is especially important for people with AML, who have already received so much chemotherapy that they barely have enough T cells for us to engineer,” Dr. Geyer says. “Because we don’t need to give the patients as many cells, it also means we are able to treat them much more quickly — we don’t have to wait to grow tens or hundreds of millions of cells in the lab.”
What Are the Next Steps To Develop CAR T for AML?
This research is still at an early stage. Three of the five patients in the pilot study responded to the treatment, meaning the CAR T cells effectively eradicated the AML cells in their bodies. Unfortunately, all five patients later died from the long-term complications of their previous AML treatments, including infections, or from disease relapse.
The team says that because all the research was done at MSK, it is allowing them to make much more significant advances in this field.
“For the patients in the study, we were able to collect samples from them and study their biology in real time,” Dr. De Wolf says. “This helps us to really understand the mechanisms of what’s going on in these patients.”
The pilot study has expanded into a larger phase 1 trial, and additional patients have been treated since this initial group of five patients completed treatment.