LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1

By S. Hacein-Bey-Abina, C. Kalle, M. Schmidt, M. McCormack, N. Wulffraat, P. Leboulch, A. Lim, Cameron S. Osborne, R. Pawliuk, Estelle Morillon and 25 more. Science, 2003

3,689 citations recorded by the source corpus.

Subfields: Genetics, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/bdf70f2c9e6db4f5884c82afd17c8be866a0de1e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Neal G. Copeland
2. C. Dunbar
3. Nancy A. Jenkins
4. S. Yamanaka
5. D. Carroll
6. M. Kay
7. L. Naldini
8. David R. Liu

In Oncology

1. C. Dunbar
2. M. Kay
3. K. Loh
4. David R. Liu
5. S. Yamanaka

Citations in the corpus

• Gene targeting using zinc finger nucleases (2005, background): “Despite limitations of this approach—immunological reaction to the virus, long-term silencing of the therapeutic gene and insertional mutagenesis—and some well-publicized setback”
• Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. (2008, methodology): “We previously reported the occurrence of lymphoproliferative diseases in 2 patients, P4 and P5, in our SCID-X1 gene therapy trial (5).”
• Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient (2009, background): “]. The occurrence of a donor origin brain tumor in the patient described here provides the first proof that the concerns raised are valid. Any innovative therapeutic approach carries predictable and unpredictable risks. For example the impressive success of gene therapy for children suffering from S”
• Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration (2006, background): “Unfortunately, in one trial of X-linked severe combined immunodeficiency (SCID) gene therapy, some treated subjects developed leukemia caused by the clonal outgrowth of transduced cell”
• CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future (2020, background): “Further investigation revealed integration of the therapeutic gene into the LMO2 protooncogene locus, presumably resulting in the development of leukemia (12).”
• Risk factors in the development of stem cell therapy (2011, background): “The use of retroviruses and lentiviruse sr aises safety issues similar to those that have been observed in the gene therapy of patients with X-linked severe combined immunodeficiency for which the occurrence of cancer has been reported due to integration of therapeutic vectors activating oncogenes [”
• Gene therapy clinical trials worldwide to 2012 – an update (2013, background): “integration near the LMO2 proto-oncogene promoter, a phenomenon known as insertional mutagenesis, leading to aberrant transcription and expression of LMO2 [10,11].”
• State-of-the-art gene-based therapies: the road ahead (2011, methodology): “The success of the gene therapy was tempered by the fact that 5 out of the 20 patients who were successfully treated for this type of SCID developed leukaemia; this was due to the clonal expansion of haematopoietic-cell-derived cells containing an integration of the proviral retrovirus and the activ”
• Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery (2007, background): “Transformed cell growth was consequent to oncogene activation at the site of vector integratio”