Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Immunology

Intrinsically disordered domains expand the CAR T cell toolbox

Nature Chemical Biology (2025)Cite this article

Subjects

A Publisher Correction to this article was published on 14 November 2025

This article has been updated

A study establishes intrinsically disordered regions (IDRs) as a new module in chimeric antigen receptor (CAR) engineering. The intrinsic biophysics of IDRs — transient, multivalent interactions — can be exploited to optimize CAR T cell therapies via enhanced clustering and synapse formation where conventional approaches fall short.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The advances of CAR T cells incorporating IDR domains.

Change history

References

  1. Demetriou, P. et al. Nat. Immunol. 21, 1232–1243 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dong, R. et al. EMBO J. 39, e104730 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gudipati, V. et al. Nat. Immunol. 21, 848–856 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Davenport, A. J. et al. Proc. Natl Acad. Sci. USA 115, E2068–E2076 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Xu, X. et al. Immunity 57, 2755–2771.8 (2024).

    Article  CAS  PubMed  Google Scholar 

  6. Zhang, X. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-025-02031-x (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Xiao, Q., McAtee, C. K. & Su, X. Nat. Rev. Immunol. 22, 188–199 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Wu, K. et al. Science 389, eadr8063 (2025).

    Article  CAS  PubMed  Google Scholar 

  9. Ginell, G. M. et al. Science 388, eadq8381 (2025).

    Article  CAS  PubMed  Google Scholar 

  10. Case, L. B., Ditlev, J. A. & Rosen, M. K. Annu. Rev. Biophys. 48, 465–494 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Driver, M. D. & Onck, P. R. Nat. Commun. 16, 3087 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA

    Tristan Yoder, Elizabeth A. Mills & Wan-Lin Lo

Authors
  1. Tristan Yoder
    View author publications

    Search author on:PubMed Google Scholar

  2. Elizabeth A. Mills
    View author publications

    Search author on:PubMed Google Scholar

  3. Wan-Lin Lo
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Wan-Lin Lo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoder, T., Mills, E.A. & Lo, WL. Intrinsically disordered domains expand the CAR T cell toolbox. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-025-02060-6

Download citation

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41589-025-02060-6

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing