Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation Journal Article
| Authors: | Boulad, F.; Wang, X.; Qu, J.; Taylor, C.; Ferro, L.; Karponi, G.; Bartido, S.; Giardina, P.; Heller, G.; Prockop, S. E.; Maggio, A.; Sadelain, M.; Riviere, I. |
| Article Title: | Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation |
| Abstract: | We conducted a pilot trial to investigate the safety and effectiveness of mobilizing CD34+ hematopoietic progenitor cells (HPCs) in adults with β-thalassemia major. We further assessed whether thalassemia patient CD34+ HPCs could be transduced with a globin lentiviral vector under clinical conditions at levels sufficient for therapeutic implementation. All patients tolerated granulocyte colony-stimulating factor well with minimal side effects. All cell collections exceeded 8 × 106 CD34+ cells/kg. Using clinical grade TNS9.3.55 vector, we demonstrated globin gene transfer averaging 0.53 in 3 validation runs performed under current good manufacturing practice conditions. Normalized to vector copy, the vector-encoded β-chain was expressed at a level approximating normal hemizygous protein output. Importantly, stable vector copy number (0.2-0.6) and undiminished vector expression were obtained in NSG mice 6 months posttransplant. Thus, we validated a safe and effective procedure for β-globin gene transfer in thalassemia patient CD34+ HPCs, which we will implement in the first US trial in patients with severe inherited globin disorders. © 2014 by The American Society of Hematology. |
| Keywords: | adult; clinical article; protein expression; human cell; hydroxyurea; nonhuman; mouse; cd34 antigen; neutrophil count; animal experiment; animal model; hemoglobin; hemoglobin blood level; gene transfer; hemoglobin beta chain; lentivirus vector; globin gene; stem cell mobilization; anxiety; hematopoietic stem cell; leukocyte count; granulocyte colony stimulating factor; expression vector; thalassemia major; leukapheresis; good manufacturing practice; human; priority journal; article; hemoglobin alpha chain |
| Journal Title: | Blood |
| Volume: | 123 |
| Issue: | 10 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2014-03-06 |
| Start Page: | 1483 |
| End Page: | 1486 |
| Language: | English |
| DOI: | 10.1182/blood-2013-06-507178 |
| PROVIDER: | scopus |
| PMCID: | PMC3945860 |
| PUBMED: | 24429337 |
| DOI/URL: | |
| Notes: | Export Date: 1 May 2014 -- CODEN: BLOOA -- Source: Scopus |
