Evidence map›Paper›PMID 41903534›Full record

ArticleCell systems2026

NOT-gated chimeric antigen receptor circuits in T and NK cells.

Seunghee Lee, Jingyao Chen, Menna Y Siddiqui, Jaehoon Choi, Joey Huang, Derrick Lee, Chen-Ting Lee, Niran Almudhfar, Mengxi Tian, Andrew Banicki and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Seunghee LeeDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Jingyao ChenDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Menna Y SiddiquiDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Jaehoon ChoiDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Joey HuangDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Derrick LeeSenti Biosciences, South San Francisco, CA, USA.
Chen-Ting LeeSenti Biosciences, South San Francisco, CA, USA.
Niran AlmudhfarSenti Biosciences, South San Francisco, CA, USA.
Mengxi TianSenti Biosciences, South San Francisco, CA, USA.
Andrew BanickiSenti Biosciences, South San Francisco, CA, USA.
Marcela Guzmán AyalaSenti Biosciences, South San Francisco, CA, USA.
Russell GordleySenti Biosciences, South San Francisco, CA, USA.
Tim K LuSenti Biosciences, South San Francisco, CA, USA.
Nicholas W FrankelSenti Biosciences, South San Francisco, CA, USA. Electronic address: nicholas.frankel@sentibio.com.
Wilson W WongDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA. Electronic address: wilwong@bu.edu.

Funding

Synthetic toolkit for precision gene expression control and signal processing in mammalian cellsR01EB029483 · NIBIB · HARVARD UNIVERSITY · PI Ahmad Samir Khalil · 2020 to 2026
$5.0M
Precise tumor targeting with logic CAR circuitsU01CA265713 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI COLSON, YOLONDA L, GRINSTAFF, MARK W. · 2021 to 2025
$2.5M
Synthetically Reengineered T cells as the Next Generation of Smart Cancer TherapyDP2CA186574 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI WONG, WILSON · 2013 to 2013
$2.5M
In Vivo Imaging Analysis System - Xenogen IVIS SpectrumS10RR024523 · NCRR · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GERSTENFELD, LOUIS CHARLES · 2008 to 2008
$350k
NCI NIH HHS DP2 CA186574NCI NIH HHS U01 CA265713NCRR NIH HHS S10 RR024523NIBIB NIH HHS R01 EB029483
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cells are powerful cancer immunotherapies, but the lack of tumor-specific single antigens for most cancers limits the therapeutic window. A NOT-gated CAR circuit, consisting of an activating CAR (aCAR) and an inhibitory CAR (iCAR), is particularly powerful because it enables new sets of antigens to be used in tumor targeting. We systematically evaluated more than 60 pairs of NOT-gated CAR circuits. Different inhibitory dose-response characteristics were observed depending on the CD3ζ signaling domain on the aCAR. Furthermore, LIR1-iCAR-expressing T cells display fewer exhaustion phenotypes. Mechanistic studies have shown that SHP-1 is the major intracellular regulator of LIR1-iCAR and the iCAR function in cis. Several of the NOT-gated circuits developed in T cells were functionally transferred into primary natural killer (NK) cells. Our NOT-gated CAR circuits provide a precise targeting strategy for safer and more effective cancer immunotherapies.

Indexed as

Killer Cells, NaturalReceptors, Chimeric AntigenT-LymphocytesAnimalsHumansImmunotherapyImmunotherapy, AdoptiveNeoplasmsSignal TransductionReceptors, Chimeric Antigenchimeric antigen receptorgene circuitslogic gatingnatural killer cellNOT gateon-target/off-tumor toxicitytherapeutic windowtumor-associated antigenstumor heterogeneity

Identifiers

PMID41903534
PMCPMC13308192

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.