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Comment
. 2022 Oct;43(10):804-805.
doi: 10.1016/j.tips.2022.04.001. Epub 2022 Apr 28.

SEAKER cells coordinate cellular immunotherapy with localized chemotherapy

Isabel C Lane  1 , Max Jan  2
Affiliations
Comment

SEAKER cells coordinate cellular immunotherapy with localized chemotherapy

Isabel C Lane et al. Trends Pharmacol Sci. 2022 Oct.

Abstract

Tumor antigen escape and T cell dysfunction limit the effectiveness of chimeric antigen receptor (CAR) T cell therapies. To overcome these challenges, Gardner et al. engineered synthetic enzyme-armed killer (SEAKER) cells to coexpress a CAR and a prodrug-activating enzyme to orchestrate a dual immunologic and pharmacologic attack at the tumor site.

Keywords: cell therapy; synthetic biology.

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Conflict of interest statement

Declaration of interests None are declared.

Figures

Figure 1.
Figure 1.. Synthetic enzyme-armed killer (SEAKER) cells activate small-molecule prodrugs at the tumor site.
CAR T cells target cognate antigen-positive cells and amplify locally, but are limited by antigen escape, suppression by the tumor microenvironment, and/or intrinsic T cell dysfunction. To overcome these challenges, SEAKER cells additionally produce bacterial enzymes that unmask systemically delivered prodrugs at the tumor site. Upon prodrug treatment, even exhausted SEAKER cells are thereby able to target both antigen-positive and antigen-negative tumor cells with high concentrations of activated small-molecule drugs.
See this image and copyright information in PMC

Comment on

  • Engineering CAR-T cells to activate small-molecule drugs in situ.
    Gardner TJ, Lee JP, Bourne CM, Wijewarnasuriya D, Kinarivala N, Kurtz KG, Corless BC, Dacek MM, Chang AY, Mo G, Nguyen KM, Brentjens RJ, Tan DS, Scheinberg DA. Gardner TJ, et al. Nat Chem Biol. 2022 Feb;18(2):216-225. doi: 10.1038/s41589-021-00932-1. Epub 2021 Dec 30. Nat Chem Biol. 2022. PMID: 34969970 Free PMC article.

References

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    1. Gardner TJ et al. (2021) Engineering CAR-T cells to activate small-molecule drugs in situ. Nat Chem Biol DOI: 10.1038/s41589-021-00932-1 - DOI - PMC - PubMed

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