Evidence map›Paper›PMID 25822024›Full record

ArticleThe Journal of clinical investigation2015

Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging.

Melissa N McCracken, Dimitrios N Vatakis, Dhaval Dixit, Jami McLaughlin, Jerome A Zack, Owen N Witte

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.7field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. CAR T Cell Nanosymbionts: Revealing the Boundless Potential of a New Dyad.International journal of molecular sciences · 2024
    Review
  3. In vivo imaging of nanoparticle-labeled CAR T cells.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Molecular therapy oncolytics · 2021
    Review
  9. OncoTargets and therapy · 2020
    Article
  10. Frontiers in immunology · 2020
    Review
  11. Review
  12. New Developments in Imaging Cell-Based Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Review
  13. Antibody with Infinite Affinity for In Vivo Tracking of Genetically Engineered Lymphocytes.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018
    Article
  14. Article
  15. Article
  16. Informatics for cancer immunotherapy.Annals of oncology : official journal of the European Society for Medical Oncology · 2017
    Review
  17. Detection of immune responses after immunotherapy in glioblastoma using PET and MRI.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  18. Review
  19. Article
  20. Molecular Imaging of Immunotherapy Targets in Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2016
    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

6 authors at 2 institutions in 1 country.

Melissa N McCracken
Dimitrios N Vatakis
Dhaval Dixit
Jami McLaughlin
Jerome A Zack
Owen N Witte
University of California, Los Angeles · USHoward Hughes Medical Institute · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
Transductionally Redirected /Transcriptionally RestricteP50CA086306 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HERSCHMAN, HARVEY R. · 2000 to 2014
$29.0M
Transduction of Hematopoietic Stem Cells for Enhanced Immunotherapy of MelanomaP01CA132681 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BALTIMORE, DAVID · 2010 to 2014
$14.4M
UCLA Institute for Molecular Medicine (IMED) CoreU54CA151819 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HEATH, JAMES R. · 2010 to 2014
$12.1M
Impact of HIV infection on anti-tumor CD8 responses in vivoR21AI106472 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VATAKIS, DIMITRIOS N · 2013 to 2014
$412k
Howard Hughes Medical InstituteNCI NIH HHS P01 CA132681NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA086306NCI NIH HHS U54 CA151819NIAID NIH HHS 5P30 AI028697NIAID NIH HHS P30 AI028697NIAID NIH HHS R21 AI106472
6 · The paper itself

Abstract

Adoptive transfer of tumor-reactive T cells can successfully reduce tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported. A noninvasive method to track engineered cells with high sensitivity and resolution would allow observation of correct cell homing and/or identification of dangerous off-target locations in preclinical and clinical applications. Human deoxycytidine kinase triple mutant (hdCK3mut) is a nonimmunogenic PET reporter that was previously shown to be an effective tool to monitor whole-body hematopoiesis. Here, we engineered a construct in which hdCK3mut is coexpressed with the anti-melanoma T cell receptor F5, introduced this construct into human CD34 cells or PBMCs, and evaluated this approach in multiple immunotherapy models. Expression of hdCK3mut allowed engrafted cells to be visualized within recipient bone marrow, while accumulation of [18F]-L-FMAU in hdCK3mut-expressing T cells permitted detection of intratumoral homing. Animals that received T cells coexpressing hdCK3mut and the anti-melanoma T cell receptor had demonstrably higher signals in HLA-matched tumors compared with those in animals that received cells solely expressing hdCK3mut. Engineered T cells caused cytotoxicity in HLA/antigen-matched tumors and induced IFN-γ production and activation. Moreover, hdCK3mut permitted simultaneous monitoring of engraftment and tumor infiltration, without affecting T cell function. Our findings suggest that hdCK3mut reporter imaging can be applied in clinical immunotherapies for whole-body detection of engineered cell locations.

Indexed as

Genes, ReporterPositron-Emission TomographyAnimalsBone MarrowChemotaxis, LeukocyteCytotoxicity Tests, ImmunologicDeoxycytidine KinaseGenes, SyntheticGenetic VectorsGraft SurvivalHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHLA-A2 AntigenHumansImmunotherapyImmunotherapy, AdoptiveDeoxycytidine KinaseHLA-A2 AntigenMART-1 AntigenReceptors, Antigen, T-CellRecombinant Fusion Proteins

Identifiers

PMID25822024
PMCPMC4463193
OpenAlexW2164796758

What OpenQuestion holds

Textmetadata
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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.