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  • Review Article
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The landscape of CAR-engineered innate immune cells for cancer immunotherapy

Nature Cancer volume 6, pages 1145–1156 (2025)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells have improved the cure rate and quality of life of patients with lymphoid malignancies but have yet to demonstrate clinical benefits in solid tumors. Thus, several CAR-engineering strategies are currently being explored to overcome the functional limitations and the high cost of CAR T cells. Key among these are CAR-engineered innate immune cells, such as natural killer (NK) cells, NK T (NKT) cells, γδ T cells and macrophages. In this Review, we discuss the potential and limitations of efforts to develop and use innate immune CAR-engineered cells for cancer immunotherapy.

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Fig. 1: CAR-redirected NK cells.
Fig. 2: CAR-redirected NKT cells (CAR NKT).
Fig. 3: CAR-redirected γδ T cells.
Fig. 4: CAR-redirected macrophages.

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Acknowledgements

This work was supported by NIH National Cancer Institute R01-CA243543 (G.D.), R01-CA256898 (G.D.), R01-CA247436 (G.D.) and R01-CA247497 (B.S.).

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Author notes

  1. These authors contributed equally: Ourania Tsahouridis, Max Xu.

Authors and Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Ourania Tsahouridis, Max Xu, Feifei Song, Barbara Savoldo & Gianpietro Dotti

  2. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Barbara Savoldo

  3. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Gianpietro Dotti

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Correspondence to Gianpietro Dotti.

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Competing interests

G.D. serves on the SAB of NanoCell, Estella, Arovella and Outpace Bio. G.D. is a cofounder of Persistence Bio. G.D and B.S. hold patents in the field of CAR-engineered cells. The other authors declare no competing interests.

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Tsahouridis, O., Xu, M., Song, F. et al. The landscape of CAR-engineered innate immune cells for cancer immunotherapy. Nat Cancer 6, 1145–1156 (2025). https://doi.org/10.1038/s43018-025-01015-z

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