15 April 2020

Scientists have created a modified CAR-T cell therapy to target multiple antigens on acute lymphoblastic leukaemia (ALL) cells, in order to avoid the problem of relapse following CD19-directed immunotherapy.

Researchers led by Drs Hisham Abdel-Azim and Nabil Ahmed of Children's Hospital Los Angeles, USA, engineered a T-cell that targets not only CD19 but also CD20 and CD22 – two other B-cell proteins often found on leukaemia cells.

“It's like using a trident to attack the cancer instead of a spear,” Dr Abdel-Azim said.

Writing in the journal Leukemia, the researchers say their new CAR T-cells targeting CD-19/20/22, named TriCAR T-cells, are significantly more effective than CAR-T cells that target CD19 alone. So far, their treatment has been tested against samples donated by ALL patients in the lab and implanted into mice.

Previous trials have shown that, following CD19-directed CAR‑T cell therapy, as many as 39% of patients with B-cell ALL relapse with CD19-negative disease. The team found that their modified CAR-T cell therapy was still effective against ALL cells taken from patients with CD19-negative relapsed disease.

What’s more, the CAR-T cells appeared to be more effective ‘serial killers’ of ALL cells. “These newer CAR-T cells bind to more cancer cells and these connections are much stronger,” said Dr Abdel-Azim. “Not only do they bind better, but they are binding again and again.”

The team hopes that the early laboratory results could help in the development of a significantly more effective treatment for both primary and relapsed ALL.

Source: Fousek K, Watanabe J, Joseph SK, George A, An X, Byrd TT, Morris JS, Luong A, Martínez-Paniagua MA, Sanber K, Navai SA, Gad AZ, Salsman VS, Mathew PR, Kim HN, Wagner DL, Brunetti L, Jang A, Baker ML, Varadarajan N, Hegde M, Kim YM, Heisterkamp N, Abdel-Azim H, Ahmed N (2020) “CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression”, Leukemia, doi: 10.1038/s41375-020-0792-2

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