Current translational and clinical practices in hematopoietic cell and gene therapy

Abstract

Clinical trials over the last 15 years have demonstrated that cell and gene therapy for cancer, monogenic and infectious disease is feasible and can lead to long-term benefit for patients (1). These trials however have been limited to proof of principle and were conducted on modest numbers of patients or over long periods of time. In order for these studies to move towards standard practice and commercialization, scalable technologies for the isolation, ex vivo manipulation and delivery of these cells to patients must be developed. Additionally, regulatory strategies and clinical protocols for the collection, creation and delivery of cell products must be generated. In this article we will review recent progress in hematopoietic cell and gene therapy, describe some of the current issues facing the field and discuss clinical, technical and regulatory approaches used to navigate the road to product development.

Clinical manufacturing of CAR T cells: foundation of a promising therapy

“…Achieving sufficient numbers of cells displaying consistent quality at relatively low cost is challenging. 56–58 The quality of CAR-T cell products is subject to donor-to-donor variation but is also largely dependent on the manufacturing environment as well as the quality and availability of ancillary raw materials and reagents. The quality of CAR-T cells needs to be carefully monitored and integrated into the manufacturing process.…”

The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells

“…Under such conditions it has been observed, and confirmed herein, that the various growth factor combinations supplying the expansion culture, result in an increased total cell number but with simultaneous differentiation and maturation of the expanded population. Therefore, supplementation of the co culture with MSC, which constitute cells of the hematopoietic microenvironment, seemed an attractive alternative which would promote mainly the progenitor cell expansion (Digiusto and Kiem, ).…”

Practical Considerations in Gene Therapy for HIV Cure

“…Such strategies ultimately protect progeny CD4+ T cells and other HIV-1 susceptible cells from further viral infection and lead to the restoration of the immune function. To achieve this goal, the transgene or a combination of genes of interest is cloned into a delivery vehicle, a viral, or nonviral vector, which is then delivered efficiently into the target cells (T cells or HSPC) ex vivo [ 13 •, 14 ]. These genetically modified cells are then release tested for safety and quality control and then re-infused into the patient.…”

“…The field of gene therapy is making sustained efforts to design better strategies for efficient, safe and cost-effective gene delivery, to identify new molecular targets for improved antiviral effect, and to move toward clinical trials that test the safety and feasibility of these approaches (discussed in [ 13 •, 19 ]).…”