Gene Therapy With The Lentiviral Vector TNS9.3.55 Produces Long-Term Improvement In Severe ß-Thalassemia

GENE THERAPY WITH THE LENTIVIRAL VECTOR TNS9.3.55 PRODUCES LONG-TERM IMPROVEMENT IN SEVERE ß-THALASSEMIA

β-thalassemia is the most prevalent monogenic disease for which gene therapy with autologous hematopoietic progenitor cells (HPC) modified to express ß-globin represents a potential therapeutic option. The most relevant clinical variables influencing success of gene therapy in ß-thalassemia are patient genotype, myeloablative conditioning regimen, number and type of progenitor cells, and vector copy number (VCN).

We report the results of a safety and efficacy study of the use of gene therapy with the human globin TNS9.3.55 vector in three patients at Memorial Sloan Kettering Cancer Center between November 2012 and May 2015, with a follow-up of 5-7 years. The results of 3 patients treated and followed at Department of Hematology and Rare Diseases European Reference Network Center for Rare Hematological Diseases (Hospital Villa Sofia-V. Cervello) are reported here.

Patients underwent mobilization with GM-CSF followed by HPC collection. Cells were CD34 selected using CliniMACS Miltenyi columns, transduced with the TNS9.3.55 vector and cryopreserved. Patients were admitted and received conditioning with busulfan on days -4 and -3 and their autologous CD34+,TNS9.3.55 cells were administered intravenously in two aliquots on days 0 and +1. The patients were discharged after blood cells count recovery. The safety of the vector was yearly evaluated monitoring the occurrence of insertional oncogenesis.

The patient characteristics and transplant features are shown in table 1. Patients age was 23, 18 and 18 respectively. Patients 1 and 3 had the same ß039-IVS1,110 genotype while patient 2 had the ß039-IVS1,6 genotype. Patient 2 was previously splenectomised. Pre-transplant vector copy number (VCN) was 0.37, 0.21 and 0.3 respectively. Patients 1 and 2 received busulfan at 8 mg/Kg while patient 3 received myeloablative dose of 14 mg/Kg because of poor initial responses for patients 1 and 2. Cell doses included 12.7, 8.4, and 9.1 Favorites Advanced From To Searcheha-3067Type keyword(s), select a suggestion if any, a ABSTRACTCD34+ TNS9.3.55cells/Kg.

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