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New target for CAR T cell leukemia therapy “gives hope” to researchers at Stanford, NCI

Last August, a new leukemia therapy called CAR T-cells burst onto the national stage when it was approved by the Food and Drug Administration to treat children and young adults with acute lymphoblastic leukemia for whom all other treatments had failed. In October, the treatment was also approved to treat some types of lymphoma.

The approvals were notable not just because CAR T-cells were the first cell-based gene therapy to be approved by the FDA, but also because of the remarkable response experienced by many patients with no other options. (I had the honor of interviewing the family of one young patient who received the treatment at Lucile Packard Children's Hospital Stanford for an upcoming Stanford Medicine magazine article -- stay tuned.)

The newly approved CAR T-cell treatment works by genetically modifying a patient's own immune cells to seek out and attack leukemia cells that have a molecule called CD19 on their surface. Now Stanford oncologist Crystal Mackall, MD, and Terry Fry, MD, a pediatric hematologist and oncologist at the National Cancer Institute -- who helped to pioneered the treatment -- are reporting that another molecule, called CD22, can also serve as a useful target for the killer cells. They published their results today in Nature Immunology.

From our release:

CAR T-cell therapy relies on a patient’s own T cells — a type of immune cell that can be a powerful killing machine. Researchers genetically modify the T cells to recognize specific molecules on the cancer cells’ surfaces and kill the cells. Some long-term remissions have followed treatment with the CD19-targeted treatment. But patients whose cancer cells don’t express CD19, or which tamp down their expression to evade the treatment, either don’t respond or can relapse. Mackall and her colleagues wondered if there was another molecule on the cancer cells that could also be a good target. Her laboratory developed a novel CAR T-cell targeting CD22 to test this idea.

The physicians conducted a small, phase-1 study of 21 patients aged 7 to 30 with treatment-resistant B-cell leukemia to test the effect of CAR T-cells engineered to target CD22. Fifteen of the 21 had previously received CD19-targeted CAR T cells. Twelve patients achieved complete remission, including 11 of 15 who had received a higher dose of the cells than had the previous six.

Unfortunately, many of the patients then relapsed after a median remission length of six months. (Three patients remain in complete remission at the time of publication six, nine and 21 months after receiving the CD22-targeted therapy.) Most of those who relapsed had leukemia cells that had downregulated the expression of CD22 on their surfaces.

The researchers hope that targeting CD19 and CD22 simultaneously may result in a powerful new approach — one that cancer cells are unable to evade.

As Mackall said, “This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy. We were all a little worried that we wouldn’t find anything comparable. But this study gives hope to the idea that there may be another similar, very potent treatment.”

Mackall is associate director of the Stanford Cancer Institute and director of the Parker Institute for Cancer Immunotherapy at Stanford.

Previously: New blood cancer treatment gets FDA approval, New center to advance cancer cell therapy and Exploring the promise and challenges of cancer immunotherapy
Photo by Darren Tunnicliff

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