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  • IN BRIEF

Activating small molecules with CAR-T cells

  1. Sarah Crunkhorn
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The effectiveness of CAR-T cell therapies is challenged by variable antigen expression, T cell exhaustion and immuno-suppressive tumour microenvironments, and so far they have only been approved for B cell malignancies. Gardner et al. have developed synthetic enzyme-armed killer (SEAKER) cells — CAR-T cells engineered to secrete bacterial enzymes that activate systemically delivered inactive prodrugs at the tumour site. In mouse xenograft models, CD19-directed SEAKER cells underwent rapid expansion at the disease site and produced high levels of the activating enzyme, leading to activation of cytotoxic small molecules and enhanced anticancer activity. SEAKER cells displayed efficacy against antigen-negative cancer cells and enzyme activity persistence after T cell exhaustion.

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Nature Reviews Drug Discovery 21, 98 (2022)

doi: https://doi.org/10.1038/d41573-022-00006-4

References

  1. Gardner, T. J. et al. Engineering CAR-T cells to activate small-molecule drugs in situ. Nat. Chem. Bio. https://doi.org/10.1038/s41589-021-00932-1 (2021)

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