Review Article | Published:

Programming CAR-T cells to kill cancer

Nature Biomedical Engineeringvolume 2pages377391 (2018) | Download Citation


T cells engineered to express chimeric antigen receptors (CARs) that are specific for tumour antigens have led to high complete response rates in patients with haematologic malignancies. Despite this early success, major challenges to the broad application of CAR-T cells as cancer therapies remain, including treatment-associated toxicities and cancer relapse with antigen-negative tumours. Targeting solid tumours with CAR-T cells poses additional obstacles because of the paucity of tumour-specific antigens and the immunosuppressive effects of the tumour microenvironment. To overcome these challenges, T cells can be programmed with genetic modules that increase their therapeutic potency and specificity. In this Review Article, we survey major advances in the engineering of next-generation CAR-T therapies for haematologic cancers and solid cancers, with particular emphasis on strategies for the control of CAR specificity and activity and on approaches for improving CAR-T-cell persistence and overcoming immunosuppression. We also lay out a roadmap for the development of off-the-shelf CAR-T cells.

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This work was supported by a SU2C-St. Baldrick’s Pediatric Cancer Dream Team Translational Research Grant (SU2CAACR-DT1113). C.L.M. is a member of the Parker Institute for Cancer Immunotherapy, which supports the Stanford University Cancer Immunotherapy Program. L.L. is supported by the National Science Foundation Graduate Research Fellowship, Stanford Graduate Fellowship, and Stanford EDGE Fellowship. R.G.M. is supported by a SARC Career Development Award.

Author information


  1. Department of Bioengineering, Stanford University, Stanford, CA, USA

    • Louai Labanieh
  2. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    • Robbie G. Majzner
    •  & Crystal L. Mackall
  3. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

    • Crystal L. Mackall
  4. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    • Crystal L. Mackall


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All authors contributed to writing and editing the manuscript.

Competing interests

C.L.M. is an inventor on a patent for a CD22-directed CAR licensed by JUNO Therapeutics, receives research funding from Bluebird Bio and Obsidian Therapeutics, and serves on the advisory boards of Unum Therapeutics, GlaxoSmithKline and Vor Pharmaceuticals. L.L. and R.G.M. declare no competing interests.

Corresponding author

Correspondence to Crystal L. Mackall.

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