The centralized development of procedures to efficiently transduce CD34+ hematopoietic stem cells from patients with Thalassemia will permit standardization of procedures, facilitate the exchange of information and expertise between the 2 clinical trial sites (MSKCC &Thessaloniki), and be cost effective. Core Unit B will mainly focus on the optimization of clinical processes and on their implementation throughout the clinical trial. The staff of MSKCC will train the staff from Thessaloniki in CD34+ cell transduction procedures and will oversee the implementation of CD34+ cell transduction and biosafety testing at both clinical sites.
The specific aims of Core Unit B are to perform and/or coordinate 1) the validation of B-globin vector transduction conditions for G-CSF- and G-CSF/AMD3100-mobilized CD34+ cells from patients;2) the transduction of patient cells at MSKCC and in Thessaloniki and ensure, via training and QA oversight, that similar transduction procedures are implemented at both clinical sites. This process entails the short-term culture and transduction of CD34+ patient cells from mobilized patients with B-globin vector stocks in semi-closed systems in collaboration with the investigators of each clinical trial;3) the biosafety release testing of transduced patient CD34+ cells for both clinical sites. This includes the testing for replication-competent lentivirus and other biosafety testing in end-of-production transduced CD34+ cells;4) the collection and analysis of PBMCs and bone marrow (BM) samples at regular intervals post-infusion to ensure the molecular and biosafety monitoring of patients treated at both clinical sites. Hence, Core Unit B will determine the vector copy number in patient blood and BM samples. It will also coordinate and distribute study materials and resulting data for the vector integration site studies;5) the banking and storage of U-globin clinical vector stocks and the freezing and cell banking of IS-globin transduced CD34+ cells and clinical specimens. In addition. Core Unit B will provide expert advice and protocols for lentiviral vector production and cell transduction to other projects. It will also supply B- globin vector stocks and clinical patient samples for functional studies involving vectors'new insulators.
|Constantinou, Varnavas C; Bouinta, Asimina; Karponi, Garyfalia et al. (2017) Poor stem cell harvest may not always be related to poor mobilization: lessons gained from a mobilization study in patients with ?-thalassemia major. Transfusion 57:1031-1039|
|Gori, Jennifer L; Butler, Jason M; Kunar, Balvir et al. (2017) Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates. Stem Cells Transl Med 6:864-876|
|Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia (2016) Optimizing autologous cell grafts to improve stem cell gene therapy. Exp Hematol 44:528-39|
|Li, Li B; Ma, Chao; Awong, Geneve et al. (2016) Silent IL2RG Gene Editing in Human Pluripotent Stem Cells. Mol Ther 24:582-91|
|Karponi, Garyfalia; Psatha, Nikoletta; Lederer, Carsten Werner et al. (2015) Plerixafor+G-CSF-mobilized CD34+ cells represent an optimal graft source for thalassemia gene therapy. Blood 126:616-9|
|Vierstra, Jeff; Reik, Andreas; Chang, Kai-Hsin et al. (2015) Functional footprinting of regulatory DNA. Nat Methods 12:927-30|
|Liu, Mingdong; Maurano, Matthew T; Wang, Hao et al. (2015) Genomic discovery of potent chromatin insulators for human gene therapy. Nat Biotechnol 33:198-203|
|Qi, Heyuan; Liu, Mingdong; Emery, David W et al. (2015) Functional validation of a constitutive autonomous silencer element. PLoS One 10:e0124588|
|Polak, Paz; Karli?, Rosa; Koren, Amnon et al. (2015) Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518:360-364|
|Watts, Korashon L; Beard, Brian C; Wood, Brent L et al. (2014) No evidence of clonal dominance after transplant of HOXB4-expanded cord blood cells in a nonhuman primate model. Exp Hematol 42:497-504|
Showing the most recent 10 out of 161 publications