ArticleScience translational medicine2012
Extended survival of glioblastoma patients after chemoprotective HSC gene therapy.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Personalised therapeutic approaches to glioblastoma: A systematic review.Frontiers in medicine · 2023Pooled it
- Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients.The Journal of clinical investigation · 2014Trial
- Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.Cell stem cell · 2026Article
- Editing around the target: epitope engineering to protect stem cell grafts.Blood advances · 2026Review
- Article
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- Article
- Cell therapies against brain tumors: Clinical development and emerging prospects.Bioengineering & translational medicine · 2025Review
- Review
- Identification of clinical prognosis features and significant DNA methylation regulation in pineoblastoma.International journal of clinical oncology · 2024Article
- In vivo selection of anti-HIV-1 gene-modified human hematopoietic stem/progenitor cells to enhance engraftment and HIV-1 inhibition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The DNA Alkyltransferase Family of DNA Repair Proteins: Common Mechanisms, Diverse Functions.International journal of molecular sciences · 2023Review
- Now you see me, now you don't: New approaches to sparing nonmalignant cells from CAR T cell therapies.Med (New York, N.Y.) · 2023Article
- Cystic Glioblastoma: A Mimicker of Infection? A Case Report and Literature Review.Case reports in oncological medicine · 2023Article
- A combined treatment regimen of MGMT-modified γδ T cells and temozolomide chemotherapy is effective against primary high grade gliomas.Scientific reports · 2021Article
- In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Purification of Human CD34Molecular therapy. Methods & clinical development · 2020Article
- Multifaceted Role of PRDM Proteins in Human Cancer.International journal of molecular sciences · 2020Review
- Preoperative Prediction Nomogram Based on Integrated Profiling for Glioblastoma Multiforme in Glioma Patients.Frontiers in oncology · 2020Article
- Autologous, Gene-Modified Hematopoietic Stem and Progenitor Cells Repopulate the Central Nervous System with Distinct Clonal Variants.Stem cell reports · 2019Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Chemotherapy with alkylating agents for treating malignant disease results in myelosuppression that can significantly limit dose escalation and potential clinical efficacy. Gene therapy using mutant methylguanine methyltransferase (P140K) gene-modified hematopoietic stem and progenitor cells may circumvent this problem by abrogating the toxic effects of chemotherapy on hematopoietic cells. However, this approach has not been evaluated clinically. Here, we show efficient polyclonal engraftment of autologous P140K-modified hematopoietic stem and progenitor cells in three patients with glioblastoma. Increases in P140K-modified cells after transplant indicate selection of gene-modified hematopoietic repopulating cells. Longitudinal retroviral integration site (RIS) analysis identified more than 12,000 unique RISs in the three glioblastoma patients, with multiple clones present in the peripheral blood of each patient throughout multiple chemotherapy cycles. To assess safety, we monitored RIS distribution over the course of chemotherapy treatments. Two patients exhibited emergence of prominent clones harboring RISs associated with the intronic coding region of PRDM16 (PR domain-containing 16) or the 3' untranslated region of HMGA2 (high-mobility group A2) genes with no adverse clinical outcomes. All three patients surpassed the median survival for glioblastoma patients with poor prognosis, with one patient alive and progression-free more than 2 years after diagnosis. Thus, transplanted P140K-expressing hematopoietic stem and progenitor cells are chemoprotective, potentially maximizing the drug dose that can be administered.
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Registered trials
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.