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Preclinical studies for a phase 1 clinical trial of autologous hematopoietic stem cell gene therapy for sickle cell disease
| Content Provider | Scilit |
|---|---|
| Author | Urbinati, Fabrizia Wherley, Jennifer Geiger, Sabine Fernandez, Beatriz Campo Kaufman, Michael L. Cooper, Aaron Romero, Zulema Marchioni, Filippo Reeves, Lilith Read, Elizabeth Nowicki, Barbara Grassman, Elke Viswanathan, Shivkumar Wang, Xiaoyan Hollis, Roger P. Kohn, Donald B. |
| Copyright Year | 2017 |
| Description | Journal: Cytotherapy Background aims Gene therapy by autologous hematopoietic stem cell transplantation (HSCT) represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials. Methods Data are shown to evaluate and establish the feasibility of isolating, transducing with the $Lenti/β^{AS3}$-FB vector and cryopreserving $CD34^{+}$ cells from human bone marrow (BM) at clinical scale. In vitro and in vivo characterization of the FCP was performed, showing that all the release criteria were successfully met. In vivo toxicology studies were conducted to evaluate potential toxicity of the $Lenti/β^{AS3}$-FB LV in the context of a murine BM transplant. Results Primary and secondary transplantation did not reveal any toxicity from the lentiviral vector. Additionally, vector integration site analysis of murine and human BM cells did not show any clonal skewing caused by insertion of the $Lenti/β^{AS3}$-FB vector in cells from primary and secondary transplanted mice. Conclusions We present here a complete protocol, thoroughly optimized to manufacture, characterize and establish safety of a FCP for gene therapy of SCD. |
| Related Links | http://www.isct-cytotherapy.org/article/S1465324917306011/pdf |
| Ending Page | 1112 |
| Page Count | 17 |
| Starting Page | 1096 |
| ISSN | 14653249 |
| e-ISSN | 14772566 |
| DOI | 10.1016/j.jcyt.2017.06.002 |
| Journal | Cytotherapy |
| Issue Number | 9 |
| Volume Number | 19 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-07-18 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cytotherapy Biochemical Research Gene Therapy Hematopoietic Stem Cells Lentiviral Vectors Sickle Cell Disease |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Immunology and Allergy Transplantation Cancer Research Immunology Genetics (clinical) Oncology |
