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Cancer immunology

Engineered γδ T cells show promise in bone tumours

Nature Reviews Immunology volume 24, page 458 (2024)Cite this article

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Adoptive cellular therapies have had limited success in the treatment of solid tumours. Fowler et al. show that γδ T cells, engineered to secrete a tumour-targeting opsonin as well as an IL-15 superagonist, can control tumour growth in a xenograft mouse model of osteosarcoma.

Human Vγ9Vδ2 T cells have potent innate anti-tumour activity and kill cancer cells via antibody-dependent cytotoxicity (ADCC). To enhance this activity, the authors inserted a secreted fusion protein, composed of antibody heavy- and light-chain variable regions fused to a heavy-chain constant region and directed against the GD2 tumour antigen, which acts as an opsonin, as well as an IL-15Rα–IL-15 fusion protein that acts as mitogen. In mice with an orthotopic xenograft of patient-derived osteosarcoma, these cells outperformed unmodified γδ T cells and binder-matched chimeric antigen receptor (CAR) αβ T cells. Their efficacy was further enhanced by zoledronic acid, an approved bisphosphonate drug for bone cancer.

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References

Original article

  • Fowler, D. et al. Payload-delivering engineered γδ T cells displayenhanced cytotoxicity, persistence, and efficacy inpreclinical models of osteosarcoma. Sci. Transl. Med. 16, eadg9814 (2024)

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Alexandra Flemming

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  1. Alexandra Flemming
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Correspondence to Alexandra Flemming.

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Flemming, A. Engineered γδ T cells show promise in bone tumours. Nat Rev Immunol 24, 458 (2024). https://doi.org/10.1038/s41577-024-01056-y

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  • DOI: https://doi.org/10.1038/s41577-024-01056-y

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