Ex vivo transduced autologous human CD34+ hematopoietic stem cells for treatment of cystinosis

We showed in the mouse model of cystinosis that bone marrow stem cells, especially the hematopoietic stem cells (HSCs), holds great promise to treat cystinosis. Because the use of allogeneic (foreign) HSCs is very risky, our goal is to develop an autologous HSC transplantation for cystinosis, i.e. the use of the patients’ own stem cells, that will be gene-corrected to introduce a functional CTNS gene using a lentiviral vector (safe version of an HIV-derived vector). The overall objective of this project is to complete the definitive preclinical and manufacturing studies, and to submit an Investigational New Drug (IND) application to support a Phase 1 clinical trial, which will be a first-in-human autologous stem cell and gene therapy treatment strategy for Cystinosis. The clinical trial will be conducted at the University of California, San Diego (UCSD)   Operational Milestone # 1, Production of Large-scale Good Manufacturing Practice (GMP, i.e. qualify for human use) pCCL-CTNS Lentiviral Vector preparation was completed on March 15, 2017. All the release testing assays were well within the acceptable range and Certificates of Analysis were provided by Indiana University Vector Production Facility (IUVPF). Tittering and characterization of the GMP pCCL-CTNS have also been completed. The final clinical grade GMP product was divided into two halves and were shipped to UCLA (where the gene-correction of the cells will occur for the clinical trial) and BioStorage Technologies to be stored in -80C freezers. The final product was received at UCLA on February 28, 2017 and at BioStorage Technologies, Inc. on March 15, 2017 and both were in good, acceptable conditions at the time of receipt. This GMP virus preparation will be used during the phase I clinical trial.   Operational Milestone # 2 which is to complete Technology Transfer and GMP Process Validation between UCSD and UCLA has begun.