Evidence map›Paper›PMID 22627392›Full record

ArticleCancer gene therapy2012

In vivo selection of autologous MGMT gene-modified cells following reduced-intensity conditioning with BCNU and temozolomide in the dog model.

J L Gori, B C Beard, C Ironside, G Karponi, H-P Kiem

Open access · bronzeAbstract read
In one paragraph

Article in Cancer gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Trial
  2. bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Molecular therapy. Advances · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Human gene therapy · 2021
    Article
  10. Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018
    Review
  11. A CombinedMolecular therapy. Methods & clinical development · 2018
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. 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

5 authors at 2 institutions in 1 country.

J L GoriClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
B C Beard
C Ironside
G Karponi
H-P Kiem
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

UNRELATED AND HLA-MISMATCHED RELATED DONOR TRANSPLANTSP01HL036444 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI RAWLINGS, DAVID J · 1986 to 2010
$25.9M
CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HEIMFELD, SHELLY · 1999 to 2014
$14.9M
MGMT-Mediated in vivo Selection in a Large Animal ModelR01HL074162 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2003 to 2006
$1.7M
NHLBI NIH HHS P01 HL036444NHLBI NIH HHS P01HL036444NHLBI NIH HHS R01 HL074162NHLBI NIH HHS R01HL074162NIDDK NIH HHS P30 DK056465NIDDK NIH HHS P30DK056465
6 · The paper itself

Abstract

Chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ) is commonly used for the treatment of glioblastoma multiforme (GBM) and other cancers. In preparation for a clinical gene therapy study in patients with glioblastoma, we wished to study whether these reagents could be used as a reduced-intensity conditioning regimen for autologous transplantation of gene-modified cells. We used an MGMT(P140K)-expressing lentivirus vector to modify dog CD34(+) cells and tested in four dogs whether these autologous cells engraft and provide chemoprotection after transplantation. Treatment with O(6)-benzylguanine (O6BG)/TMZ after transplantation resulted in gene marking levels up to 75%, without significant hematopoietic cytopenia, which is consistent with hematopoietic chemoprotection. Retrovirus integration analysis showed that multiple clones contribute to hematopoiesis. These studies demonstrate the ability to achieve stable engraftment of MGMT(P140K)-modified autologous hematopoietic stem cells (HSCs) after a novel reduced-intensity conditioning protocol using a combination of BCNU and TMZ. Furthermore, we show that MGMT(P140K)-HSC engraftment provides chemoprotection during TMZ dose escalation. Clinically, chemoconditioning with BCNU and TMZ should facilitate engraftment of MGMT(P140K)-modified cells while providing antitumor activity for patients with poor prognosis glioblastoma or alkylating agent-sensitive tumors, thereby supporting dose-intensified chemotherapy regimens.

Indexed as

DNA Modification MethylasesDNA Repair EnzymesHematopoietic Stem Cell TransplantationTumor Suppressor ProteinsAnimalsCarmustineDacarbazineDogsGenetic TherapyGlioblastomaHematopoiesisHumansLentivirusTemozolomideTransplantation ConditioningCarmustineDacarbazineDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTemozolomideTumor Suppressor Proteins

Identifiers

PMID22627392
PMCPMC3466091
OpenAlexW2166729107

What OpenQuestion holds

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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.