Evidence map›Paper›PMID 23931270›Full record

ArticleHuman gene therapy methods2013

Potential limitations of the NSG humanized mouse as a model system to optimize engineered human T cell therapy for cancer.

Erik M Alcantar-Orozco, Hannah Gornall, Vania Baldan, Robert E Hawkins, David E Gilham

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy methods, 2013. 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
1.6field-weighted citation impact, top 17% 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, 41 citations in OpenAlex.

  1. LRRC15-CAR T Cells for the Treatment of Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  2. Article
  3. Review
  4. Characterization of a xenograft model for anti-CD19 CAR T cell studies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  12. Humanized mice for immune checkpoint blockade in human solid tumors.American journal of clinical and experimental urology · 2019
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Next-Generation Chimeric Antigen Receptor T-Cell Therapy: Going off the Shelf.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2017
    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

5 authors at 2 institutions in 1 country.

Erik M Alcantar-OrozcoClinical and Experimental Immunotherapy Group, Department of Medical Oncology, The Institute of Cancer Sciences, Manchester Academic Healthcare Science Centre, The University of Manchester , Manchester M20 4BX, United Kingdom .
Hannah Gornall
Vania Baldan
Robert E Hawkins
David E Gilham
Manchester Academic Health Science Centre · GBCancer Research UK Manchester Institute · GB

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UKMedical Research Council MR/K500732/1
6 · The paper itself

Abstract

The genetic modification of peripheral blood lymphocytes using retroviral vectors to redirect T cells against tumor cells has been recently used as a means to generate large numbers of antigen-specific T cells for adoptive cell therapy protocols. However, commonly used retroviral vector-based genetic modification requires T cells to be driven into cell division; this potent mitogenic stimulus is associated with the development of an effector phenotype that may adversely impact upon the long-term engraftment potential and subsequent antitumor effects of T cells. To investigate whether the cytokines used during culture impact upon the engraftment potential of gene-modified T cells, a humanized model employing T cells engrafted with a MART-1-specific T cell receptor adoptively transferred into NOD/Shi-scid IL-2rγ(-/-) (NSG) immune-deficient mice bearing established melanoma tumors was used to compare the effects of the common γ chain cytokines IL-2, IL-7, and IL-15 upon gene-modified T cell activity. MART-1-specific T cells cultured in IL-7 and IL-15 demonstrated greater relative in vitro proliferation and viability of T cells compared with the extensively used IL-2. Moreover, the IL-15 culture prolonged the survival of animals bearing melanoma tumors after adoptive transfer. However, the combination of IL-7 and IL-15 produced T cells with improved engraftment potential compared with IL-15 alone; however, a high rate of xenogeneic graft-versus-host disease prevented the identification of a clear improvement in antitumor effect of these T cells. These results clearly demonstrate modulation of gene-modified T cell engraftment in the NSG mouse, which supports the future testing of the combination of IL-7 and IL-15 in adoptive cell therapy protocols; however, this improved engraftment is also associated with the long-term maintenance of xenoreactive T cells, which limits the ultimate usefulness of the NSG mouse model in this situation.

Indexed as

AnimalsCell Line, TumorCell ProliferationCells, CulturedHumansImmunotherapy, AdoptiveInterleukinsMART-1 AntigenMelanomaMiceMice, Inbred NODMice, SCIDModels, AnimalSkin NeoplasmsT-LymphocytesXenograft Model Antitumor AssaysInterleukinsMART-1 Antigen

Identifiers

PMID23931270
PMCPMC3798231
OpenAlexW2112118837

What OpenQuestion holds

Textmetadata
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.