Evidence map›Paper›PMID 25605948›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Genetic engineering of hematopoietic stem cells to generate invariant natural killer T cells.

Drake J Smith, Siyuan Liu, Sunjong Ji, Bo Li, Jami McLaughlin, Donghui Cheng, Owen N Witte, Lili Yang

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
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  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Novel Immunotherapies for Osteosarcoma.Frontiers in oncology · 2022
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Methods for Studying Mouse and Human Invariant Natural Killer T Cells.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  20. Creatine uptake regulates CD8 T cell antitumor immunity.The Journal of experimental medicine · 2019
    Article
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

8 authors.

Drake J SmithEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and.
Siyuan LiuEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and.
Sunjong JiEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and.
Bo LiEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and.
Jami McLaughlinDepartment of Microbiology, Immunology and Molecular Genetics, and.
Donghui ChengEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
Owen N WitteEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095 liliyang@ucla.edu owenwitte@mednet.ucla.edu.
Lili YangEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Department of Microbiology, Immunology and Molecular Genetics, and liliyang@ucla.edu owenwitte@mednet.ucla.edu.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Stem Cell-Engineered Invariant Natural Killer T Cells for Cancer TherapyDP2CA196335 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, LILI · 2014 to 2014
$2.3M
Howard Hughes Medical InstituteNCI NIH HHS DP2 CA196335NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA092131NCI NIH HHS T32 CA009120
6 · The paper itself

Abstract

Invariant natural killer T (iNKT) cells comprise a small population of αβ T lymphocytes. They bridge the innate and adaptive immune systems and mediate strong and rapid responses to many diseases, including cancer, infections, allergies, and autoimmunity. However, the study of iNKT cell biology and the therapeutic applications of these cells are greatly limited by their small numbers in vivo (∼0.01-1% in mouse and human blood). Here, we report a new method to generate large numbers of iNKT cells in mice through T-cell receptor (TCR) gene engineering of hematopoietic stem cells (HSCs). We showed that iNKT TCR-engineered HSCs could generate a clonal population of iNKT cells. These HSC-engineered iNKT cells displayed the typical iNKT cell phenotype and functionality. They followed a two-stage developmental path, first in thymus and then in the periphery, resembling that of endogenous iNKT cells. When tested in a mouse melanoma lung metastasis model, the HSC-engineered iNKT cells effectively protected mice from tumor metastasis. This method provides a powerful and high-throughput tool to investigate the in vivo development and functionality of clonal iNKT cells in mice. More importantly, this method takes advantage of the self-renewal and longevity of HSCs to generate a long-term supply of engineered iNKT cells, thus opening up a new avenue for iNKT cell-based immunotherapy.

Indexed as

Genetic EngineeringAdoptive TransferAnimalsBase SequenceDNAHematopoietic Stem CellsLung NeoplasmsMelanoma, ExperimentalMiceMolecular Sequence DataNatural Killer T-CellsReceptors, Antigen, T-CellSequence Homology, Nucleic AcidDNAReceptors, Antigen, T-Cellgenetic engineeringhematopoietic stem cellsHSCsiNKT cellsinvariant natural killer T cells

Identifiers

PMID25605948
PMCPMC4321292

What OpenQuestion holds

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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.