This Program Project Grant (PO1) explores the enhancement of cord blood transplantation by employing ex-vivo expansion of cord blood stem/progenitor and T cells in preclinical studies and clinical trials. All four projects will undertake clinical trials during the course of the studies. These rely on the availability of a GMP manufacturing facility for the preparation of the cellular therapy products and associated viral vectors. Projects 1 and 4 will use on the Good Manufacturing Practice (GMP) Facility at MD Anderson Cancer Center (MDACC) and Projects 2 and 3 will rely on the GMP facility and the Clinical Vector Production Facility at the Center for Cell and Gene Therapy Baylor College of Medicine (BCM). The GMP Facilities at BCM and MDACC have been in operation for more than 10 years. The Cell Processing Facilities at both institutions have considerable experience in the preparation of a wide variety of cellular products, including all that would be required for the Projects in this application. Both facilities consist of HEPA filtered. Class 10,000 space divided into multiple cell preparation laboratories, low temperature storage areas, cell sorting and analysis laboratories, large equipment areas and central supply facilities. Both Facilities are well equipped to operate under GMP conditions, with extensive documentation systems, barcoding, environmental monitoring and quality assurance, control and improvement programs. Additional components of the Core are the Quality Control Laboratories at BCM and MDACC, which perform in-house testing of cellular products (and vectors), and are responsible for routine monitoring of Good Manufacturing Practices; and the Quality Assurance Group to ensure compliance with GMP and provides independent overview of all aspects of manufacturing and release. The Clinical Vector Production Facility at BCM, which is also a part of the Core, has produced more than 30 clinical grade adenovectors and retroviral vectors for local, national and international studies. The GMP staff at both institutions have extensive regulatory experience that will facilitate the translational of laboratory studies into clinical trials. In summary, the GMP Laboratory Core is a vital component of the P01 that will provide essential services to the implementation of the clinical studies in Projects 1, 2, 3 and 4.
Cord blood (CB) has emerged as an important source of stem cells for patients lacking HLA-matched donors. However, the major disadvantage of CB is the low stem and progenitor cell dose resulting in delayed engraftment and immune reconstitution. In this PO1 we have developed strategic approaches including the ex vivo expansion of CB stem/progenitor and T cells to overcome the limitations of CB transplant. This Core will manufacture cellular therapy products and clinical grade vectors required for the clinical trials in this PO1.
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