Evidence map›Paper›PMID 32094195›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Joint profiling of chromatin accessibility and CAR-T integration site analysis at population and single-cell levels.

Wenliang Wang, Maria Fasolino, Benjamin Cattau, Naomi Goldman, Weimin Kong, Megan A Frederick, Sam J McCright, Karun Kiani, Joseph A Fraietta, Golnaz Vahedi

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.9field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

10 authors at 2 institutions in 1 country.

Wenliang WangDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Maria FasolinoDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Benjamin CattauDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Naomi GoldmanDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Weimin KongDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Megan A FrederickDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Sam J McCrightDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.ORCID 0000-0002-4295-9290
Karun KianiDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Joseph A FraiettaDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Golnaz VahediDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; vahedi@pennmedicine.upenn.edu.
University of Pennsylvania · USParker Institute for Cancer Immunotherapy · US

Funding

Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Joseph Anthony Fraietta · 2017 to 2026
$26.8M
Linking insertional mutagenesis and cell function to improve CAR T cell therapyR01CA241762 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D, MELENHORST, JAN J · 2019 to 2023
$3.1M
Critical role of TCF-1 on the epigenetic identity of memory T cellsR01HL145754 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI VAHEDI, GOLNAZ · 2019 to 2023
$2.3M
Determinants of CD8+ T Cell Aging and Reduced Function in B Cell CancerU01AG066100 · NIA · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2019 to 2020
$243k
NCI NIH HHS P01 CA214278NCI NIH HHS R01 CA241762NHLBI NIH HHS R01 HL145754NIA NIH HHS U01 AG066100
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T immunotherapy has yielded impressive results in several B cell malignancies, establishing itself as a powerful means to redirect the natural properties of T lymphocytes. In this strategy, the T cell genome is modified by the integration of lentiviral vectors encoding CAR that direct tumor cell killing. However, this therapeutic approach is often limited by the extent of CAR-T cell expansion in vivo. A major outstanding question is whether or not CAR-T integration itself enhances the proliferative competence of individual T cells by rewiring their regulatory landscape. To address this question, it is critical to define the identity of an individual CAR-T cell and simultaneously chart where the CAR-T vector integrates into the genome. Here, we report the development of a method called EpiVIA (https://github.com/VahediLab/epiVIA) for the joint profiling of the chromatin accessibility and lentiviral integration site analysis at the population and single-cell levels. We validate our technique in clonal cells with previously defined integration sites and further demonstrate the ability to measure lentiviral integration sites and chromatin accessibility of host and viral genomes at the single-cell resolution in CAR-T cells. We anticipate that EpiVIA will enable the single-cell deconstruction of gene regulation during CAR-T therapy, leading to the discovery of cellular factors associated with durable treatment.

Indexed as

ChromatinEpigenesis, GeneticImmunotherapy, AdoptiveT-LymphocytesClone CellsGenetic TestingGenome, HumanHumansLentivirusProvirusesSingle-Cell AnalysisVirus IntegrationChromatinCAR-T cellepigeneticslentiviral integration sitesingle-cell genomics

Identifiers

PMID32094195
PMCPMC7071901
OpenAlexW3007769221

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.