Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation.

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 × 10(6) 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. This trial is registered at www.clinicaltrials.gov as #NCT01639690.
AuthorsFarid Boulad, Xiuyan Wang, Jinrong Qu, Clare Taylor, Leda Ferro, Garyfalia Karponi, Shirley Bartido, Patricia Giardina, Glenn Heller, Susan E Prockop, Aurelio Maggio, Michel Sadelain, Isabelle Rivière
JournalBlood (Blood) Vol. 123 Issue 10 Pg. 1483-6 (Mar 6 2014) ISSN: 1528-0020 [Electronic] United States
PMID24429337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD34
  • beta-Globins
  • Animals
  • Antigens, CD34 (metabolism)
  • Colony-Forming Units Assay
  • Disease Models, Animal
  • Erythroid Precursor Cells (metabolism)
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors (genetics)
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Heterografts
  • Humans
  • Mice
  • Transduction, Genetic
  • beta-Globins (biosynthesis, genetics)
  • beta-Thalassemia (genetics, metabolism, therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: