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.

SYNTHETIC BIOLOGY

CAR-T cells SEAK help from enzymes

Nature Chemical Biology volume 18, pages 122–123 (2022)Cite this article

Subjects

Chimeric antigen receptor T cells (CAR-T cells) are often hindered by the concurrent challenges of variable antigen expression patterns and immunosuppressive tumor microenvironments. A new approach enhances CAR-T cells by coexpressing bacterial enzymes that activate prodrugs in high concentrations at the disease site.

The clinical success of CAR-T cells against B cell malignancies has proven that immune cells engineered to recognize tumor-associated antigens can serve as a powerful new class of living medicines. However, these targeted cell therapies continue to face challenges of variable antigen expression and CAR-T cell dysfunction in the immunosuppressive tumor microenvironment (TME). Now, researchers have reinforced CAR-T cell activity with the help of bacterial enzymes that serve to locally activate chemotherapeutic prodrugs and provide an orthogonal, antigen-independent mode of attack1.

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Fig. 1: 'SEAKER' cells for dual-mode tumor lysis.

References

  1. Gardner, T. J. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-021-00932-1 (2021).

  2. Majzner, R. G. & Mackall, C. L. Cancer Discov. 8, 1219–1226 (2018).

    Article  CAS  Google Scholar 

  3. Hyrenius-Wittsten, A. & Roybal, K. T. Trends. Cancer 5, 583–592 (2019).

    Article  CAS  Google Scholar 

  4. Gardner, T. J. et al. Cancers 12, 2175 (2020).

    Article  CAS  Google Scholar 

  5. Sharma, S. K. & Bagshawe, K. D. Expert Opin. Biol. Th. 17, 1–13 (2016).

    Article  Google Scholar 

  6. Roybal, K. T. et al. Cell 167, 419–432.e16 (2016).

    Article  CAS  Google Scholar 

  7. Choi, B. D. et al. Nat. Biotechnol. 37, 1049–1058 (2019).

    Article  CAS  Google Scholar 

  8. Sukumaran, S. et al. Cancer Discov. 8, 972–987 (2018).

    Article  CAS  Google Scholar 

  9. Huang, X. et al. Nat. Nanotechnol. 16, 214–223 (2021).

    Article  CAS  Google Scholar 

  10. Park, A. K. et al. Science Transl. Med. 12, eaaz1863 (2020).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Rosa Vincent & Tal Danino

  2. Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA

    Tal Danino

  3. Data Science Institute, Columbia University, New York, NY, USA

    Tal Danino

Authors
  1. Rosa Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tal Danino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tal Danino.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vincent, R., Danino, T. CAR-T cells SEAK help from enzymes. Nat Chem Biol 18, 122–123 (2022). https://doi.org/10.1038/s41589-021-00933-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-021-00933-0

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer