Evidence map›Paper›PMID 31592660›Full record

ArticleACS synthetic biology2019

An AND-Gated Drug and Photoactivatable Cre-

Molly E Allen, Wei Zhou, Jeyan Thangaraj, Phillip Kyriakakis, Yiqian Wu, Ziliang Huang, Phuong Ho, Yijia Pan, Praopim Limsakul, Xiangdong Xu and 1 more

Open access · greenAbstract read
In one paragraph

Article in ACS synthetic biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.9field-weighted citation impact, top 12% of its field
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

27 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  6. Optogenetic engineering for precision cancer immunotherapy.Trends in pharmacological sciences · 2025
    Review
  7. Review
  8. Article
  9. Protein design accelerates the development and application of optogenetic tools.Computational and structural biotechnology journal · 2025
    Review
  10. Review
  11. Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023
    Review
  12. Article
  13. Article
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  15. Article
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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

11 authors at 2 institutions in 2 countries.

Molly E Allen
Wei ZhouChongqing Cancer Hospital , 181 Hanyu Road, Shapingba District , Chongqing 400030 , China.
Jeyan Thangaraj
Phillip Kyriakakis
Yiqian Wu
Ziliang Huang
Phuong Ho
Yijia Pan
Praopim Limsakul
Xiangdong XuDepartment of Pathology, Veterans Affairs San Diego Healthcare System , University of California, San Diego , 9500 Gilman Drive , La Jolla , California 92093-0412 , United States.
University of California San Diego · USChongqing Cancer Hospital · CN

Funding

Role of Spatiotemporal Epigenetic Dynamics in Regulating Endothelial Gene Expressions under FlowsR01HL121365 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHIEN, SHU, WANG, YINGXIAO · 2014 to 2025
$7.5M
Integrative Bioengineering of Heart, Vessels, and BloodT32HL105373 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, INTAGLIETTA, MARCOS · 2010 to 2019
$3.6M
Locus-specific Imaging of Dynamic Histone Methylations during ReprogrammingR01GM125379 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, WANG, YINGXIAO · 2017 to 2020
$2.4M
Multiplex FRET Imaging of Kinase-Epigenome Interregulations in Live Cancer CellsR33CA204704 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2017 to 2019
$1.1M
Remote-Control Mechano-Genetics and Epigenetics for Live Cell ManipulationR01GM126016 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2018 to 2020
$1.1M
Engineering Machinery Molecules to Visualize and Actuate ImmunotherapyR21CA209629 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2017 to 2018
$371k
NCI NIH HHS R21 CA209629NCI NIH HHS R33 CA204704NHLBI NIH HHS R01 HL121365NHLBI NIH HHS T32 HL105373NIGMS NIH HHS R01 GM125379NIGMS NIH HHS R01 GM126016
6 · The paper itself

Abstract

While engineered chimeric antigen receptor (CAR) T cells have shown promise in detecting and eradicating cancer cells within patients, it remains difficult to identify a set of truly cancer-specific CAR-targeting cell surface antigens to prevent potentially fatal on-target off-tumor toxicity against other healthy tissues within the body. To help address this issue, we present a novel tamoxifen-gated photoactivatable split-Cre recombinase optogenetic system, called TamPA-Cre, that features high spatiotemporal control to limit CAR T cell activity to the tumor site. We created and optimized a novel genetic AND gate switch by integrating the features of tamoxifen-dependent nuclear localization and blue-light-inducible heterodimerization of Magnet protein domains (nMag, pMag) into split Cre recombinase. By fusing the cytosol-localizing mutant estrogen receptor ligand binding domain (ERT2) to the N-terminal half of split Cre(2-59aa)-nMag, the TamPA-Cre protein ERT2-CreN-nMag is physically separated from its nuclear-localized binding partner, NLS-pMag-CreC(60-343aa). Without tamoxifen to drive nuclear localization of ERT2-CreN-nMag, the typically high background of the photoactivation system was significantly suppressed. Upon blue light stimulation following tamoxifen treatment, the TamPA-Cre system exhibits sensitivity to low intensity, short durations of blue light exposure to induce robust Cre-loxP recombination efficiency. We finally demonstrate that this TamPA-Cre system can be applied to specifically control localized CAR expression and subsequently T cell activation. As such, we posit that CAR T cell activity can be confined to a solid tumor site by applying an external stimulus, with high precision of control in both space and time, such as light.

Indexed as

Cell- and Tissue-Based TherapyCell LineCell Line, TumorCell NucleusHEK293 CellsHumansIntegrasesJurkat CellsK562 CellsOptogeneticsReceptors, Antigen, T-CellReceptors, EstrogenTamoxifenT-LymphocytesCre recombinaseIntegrasesReceptors, Antigen, T-CellReceptors, EstrogenTamoxifenCAR T cellCre-loxP recombinationERT2immunotherapynMag and pMagoptogenetics

Identifiers

PMID31592660
PMCPMC8135225
OpenAlexW2980213531

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.