Scientists engineer an extra control into CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy has been effective in treating human B cell malignancies, as well as having potential in a multitude of other cancers. However, the persistence of CAR T cells after remission of the cancer leads to an eventual depletion of healthy B cells. Now, scientists have demonstrated a strategy to prevent this by coadministering an antibody after the tumor has gone.

Dirk Busch and his colleagues at the Technical University München published their results in The Journal of Clinical Investigation.

CAR T-cell therapy has taken the arena of cancer treatment, especially B cell malignancies, by storm. CAR T cells are engineered to recognize a protein called CD19 that marks cancer cells since it’s expressed during early stages in the development of B cells. When it is administered, it therefore seeks out and destroys B-cell tumors.

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Because the engineered CAR T cells can persist after the patient has gone into remission, the chance of healthy B cells being affected by the therapy is major safety risk. A lower B cell count affects the healthy functioning of the immune system to recognize pathogens and prevent diseases.

In a mouse model of leukemia, they designed CAR T cells that also expressed a "decoy" protein called EGFR. When the treatment was successful and the cancer had been cleared by the CAR T cells, they then administered an EGFR antibody, which recognizes and block the activity of the CAR T cells.

As cell therapies advance, this preclinical study shows that multiple targeting mechanisms can be engaged to potentially control the activity (and deactivity) of the cancer therapy in humans.