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Cancer immunotherapy

When a CAR becomes a tank

Nature Reviews Drug Discovery volume 17, page 707 (2018)Cite this article

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These results open new possibilities to make T-cell therapies more effective, particularly against solid tumours

The authors had already described armoured CAR T cells, whereby CAR T cells had been modified to express immuno-modulatory ligands or to secrete cytokines. On the basis of these findings, the authors decided to use this platform to create CAR T cells that could secrete single-chain variable fragments (scFvs) of monoclonal antibodies (mAbs) that block immune checkpoint signalling. First, the authors generated second-generation CAR constructs containing domains that recognize the antigens CD19 (found on B cell malignancies) or MUC16 (expressed on ovarian and pancreatic cancer cells) fused to mouse CD28 and CD3ζ T cell signalling domains. They then modified this construct to include an scFv from an anti-mouse programmed cell death 1 (PD1) mAb and transduced primary mouse T cells with this construct.

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References

  1. Rafiq, S. et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat. Biotechnol. 36, 847–856 (2018)

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  1. M. Teresa Villanueva
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Villanueva, M. When a CAR becomes a tank. Nat Rev Drug Discov 17, 707 (2018). https://doi.org/10.1038/nrd.2018.164

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