Contributions
Abstract: S144
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:15 - 12:30
Location: Room N109
Background
Aims
To demonstrate engraftment of gene-corrected HSCs in non-conditioned Fanconi anemia patients.
Methods
To improve previous results, we proposed a new approach based on two clinical trials. First, to increase the HSC collection, we designed a trial employing a plerixafor plus G-CSF mobilization regimen. Second, to improve the quality of corrected HSCs, cells were pre-stimulated for only 8-10 hours and transduced with a new lentiviral vector (PGK-FANCA.Wpre*) for 12-14h, a substantially shorter duration than in previous trials. To avoid chemotherapy-induced damage, a conditioning regimen was not included in the trial, based on the expected proliferative advantage of autologous corrected HSCs.
Results
Eight patients have been included so far in the HSC collection trial. No severe adverse events (SAE) related to the procedure have been reported. The most relevant AE has been the transfusion of packed red blood cells and platelets. Six FA patients aged 3-6 years underwent collections after mobilization of significant numbers of CD34+ cells (10 to 70 CD34+ cells/µL) to peripheral blood. Two patients (15 and 16 years) failed to mobilize. On average, 5 million CD34+ cells/Kg were collected, with 45% recovery after immunoselection. In the first patient included in the gene therapy trial, fresh immunoselected CD34+ cells were transduced with the therapeutic vector. Subsequently, two patients, were infused with transduced CD34+ cells that remained cryopreserved for almost 2 years. Infused cell products contained 0.5 to 1.4 million CD34+ cells/kg, and vector copy numbers per cell (VCN/cell) that ranged between 0.17 to 0.45. To-date, there has been no SAE related to the procedure. Engraftment of gene corrected cells has been observed in the three patients. Notably, increased gene marking levels and significant phenotypic correction in the hematopoietic progenitor cells, deduced from the acquired resistance of the colony forming cells to mitomycin C (15% of BM CFCs survived to 10 nM MMC), have been demonstrated after 9 months of follow up in one of the patients.
Conclusion
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Lentiviral vector, Gene therapy, Fanconi anemia, Bone Marrow Failure
Abstract: S144
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:15 - 12:30
Location: Room N109
Background
Aims
To demonstrate engraftment of gene-corrected HSCs in non-conditioned Fanconi anemia patients.
Methods
To improve previous results, we proposed a new approach based on two clinical trials. First, to increase the HSC collection, we designed a trial employing a plerixafor plus G-CSF mobilization regimen. Second, to improve the quality of corrected HSCs, cells were pre-stimulated for only 8-10 hours and transduced with a new lentiviral vector (PGK-FANCA.Wpre*) for 12-14h, a substantially shorter duration than in previous trials. To avoid chemotherapy-induced damage, a conditioning regimen was not included in the trial, based on the expected proliferative advantage of autologous corrected HSCs.
Results
Eight patients have been included so far in the HSC collection trial. No severe adverse events (SAE) related to the procedure have been reported. The most relevant AE has been the transfusion of packed red blood cells and platelets. Six FA patients aged 3-6 years underwent collections after mobilization of significant numbers of CD34+ cells (10 to 70 CD34+ cells/µL) to peripheral blood. Two patients (15 and 16 years) failed to mobilize. On average, 5 million CD34+ cells/Kg were collected, with 45% recovery after immunoselection. In the first patient included in the gene therapy trial, fresh immunoselected CD34+ cells were transduced with the therapeutic vector. Subsequently, two patients, were infused with transduced CD34+ cells that remained cryopreserved for almost 2 years. Infused cell products contained 0.5 to 1.4 million CD34+ cells/kg, and vector copy numbers per cell (VCN/cell) that ranged between 0.17 to 0.45. To-date, there has been no SAE related to the procedure. Engraftment of gene corrected cells has been observed in the three patients. Notably, increased gene marking levels and significant phenotypic correction in the hematopoietic progenitor cells, deduced from the acquired resistance of the colony forming cells to mitomycin C (15% of BM CFCs survived to 10 nM MMC), have been demonstrated after 9 months of follow up in one of the patients.
Conclusion
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Lentiviral vector, Gene therapy, Fanconi anemia, Bone Marrow Failure