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Updated: Sep 14, 2025

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

Ourania Tsahouridis1, Max Xu1, Feifei Song1

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

Nature Cancer
|July 18, 2025
PubMed

Insights

Chimeric antigen receptor (CAR) T cells show promise for blood cancers but not solid tumors. This review explores using engineered innate immune cells, like NK cells, for improved cancer immunotherapy strategies.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Chimeric antigen receptor (CAR) T cells have significantly advanced lymphoid malignancy treatment.
  • CAR T cells have not yet shown comparable efficacy in solid tumors.
  • Limitations include functional constraints and high costs associated with current CAR T-cell therapies.

Purpose of the Study:

  • To review the potential and limitations of CAR-engineered innate immune cells for cancer immunotherapy.
  • To explore novel strategies beyond traditional CAR T cells for solid tumor treatment.
  • To discuss the development and application of innate immune cells in CAR-based cancer therapy.

Main Methods:

  • Review of current literature on CAR-engineered innate immune cells.
  • Analysis of strategies to overcome CAR T-cell limitations.
  • Discussion of various innate immune cell types (NK, NKT, γδ T, macrophages) for CAR engineering.

Main Results:

  • CAR-engineered innate immune cells offer a promising alternative to CAR T cells for solid tumors.
  • Natural killer (NK) cells, NK T (NKT) cells, γδ T cells, and macrophages are being explored for CAR engineering.
  • These approaches aim to enhance anti-tumor activity and address limitations of conventional CAR T cells.

Conclusions:

  • CAR-engineered innate immune cells represent a developing frontier in cancer immunotherapy.
  • Further research is needed to optimize these strategies for clinical application in solid tumors.
  • Innate immune cell-based CAR therapies hold potential for improving patient outcomes in challenging cancers.

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