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Principal Investigator: DONALD Lawrence SIEGEL
Organization: UNIVERSITY OF PENNSYLVANIA
Fiscal Year: 2020
Award: $179,023
Funding agency: National Cancer Institute
SUMMARY CORE B: GMP CELL and RNA MANUFACTURING
Core B is the Clinical Cell and Vaccine Production Facility (CVPF). The CVPF is a Foundation for the
Accreditation of Cellular Therapy (FACT)-accredited, Good Manufacturing Practices (GMP) compliant cell and
RNA manufacturing facility. This facility supports “bench to bedside” translation of innovative investigational
cell and gene biologics for a wide range of cancers, infectious diseases, and other therapeutic indications at
the University of Pennsylvania (Penn) and its collaborating institutions. The CVPF supports manufacturing for
18 investigational new drug applications (INDs), and has produced over 2400 cellular vaccines that have been
safely administered to more than 900 patients. The CVPF is designated as the Core B GMP cell and RNA
manufacturing resource for the projects outlined in this proposal, and supports a) process development and
validation experiments for successful GMP clinical translation of cell and RNA manufacturing and b) clinical
trial manufacturing and final product testing of gene modified cells for human administration. The CVPF will
provide specific support for the proposed projects through the development of protocols to manufacture (1)
tandem CD19 CAR T cell and CD22 CAR T cell products, (2) TCR negative, HLA-I negative CD19 CAR T
cells, (3) CD33 negative hematopoietic stem cells and CD33 CAR T cells, and (4) tandem CD19 CAR T cell
and BCMA CAR T cell products. To achieve effective deletion of the above mentioned targets (TCR, HLA-I,
CD33) we will manufacture GMP-grade guide RNAs and Cas9 mRNA. We will electroporate therapeutic cells
with these RNA constructs to create CRISPR/Cas9 mediate, target negative cells. Quality control assays and
release criteria will be developed for each therapeutic cell type to ensure consistent production of safe and
high quality modified cells.
Terms: <Accreditation><Allogenic><Anti-CD22><Apheresis><Assay><Autologous><B-Cell Antigen CD22><B3 antigen><Bioassay><Biologic Assays><Biological><Biological Assay><Blood Component Removal><Blood Precursor Cell><Bp35><CAR T cell therapy><CAR T cells><CAR T therapy><CD19><CD19 gene><CD20><CD22><CD22 antigen><CD22 gene><CRISPR><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/Cas method><CRISPR/Cas system><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Cancer Burden><Cancer Center><Cancers><Cas nuclease technology><Cell Body><Cell Therapy><Cells><Clinical><Clinical Trials><Clustered Regularly Interspaced Short Palindromic Repeats><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Collection><Communicable Diseases><Communities><Core Facility><Cryofixation><Cryopreservation><Development><Dose><Early-Stage Clinical Trials><Ensure><Foundations><Gene-Modified><Genes><Goals><Guide RNA><HSC transplantation><Hemapheresis><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematopoietic Cancer><Hematopoietic Progenitor Cells><Hematopoietic Stem Cell Mobilization><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Hematopoietic stem cells><Human><In Vitro><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Institution><Investigation><Investigational New Drug Application><Laboratories><Lentiviral Vector><Lentivirus Vector><Leu-16><MS4A1><MS4A1 gene><MS4A2><Malignant Hematologic Neoplasm><Malignant Neoplasms><Malignant Tumor><Mediating><Medicine><Messenger RNA><Methods><Modern Man><Mononuclear><National Cancer Burden><Non-Polyadenylated RNA><PBSC><Pathology><Patients><Pennsylvania><Peripheral Blood Stem Cell><Peripheral Stem Cells><Phase 1 Clinical Trials><Phase 2 Clinical Trials><Phase I Clinical Trials><Phase II Clinical Trials><Pheresis><Process><Production><Protocol><Protocols documentation><Quality Control><RNA><RNA Gene Products><Reagent><Research Resources><Resources><Ribonucleic Acid><SIGLEC2><Sialic Acid-Binding Immunoglobulin-Like Lectin 2><Stem Cell Mobilization><Surface><T cells for CAR><T-Cells><T-Lymphocyte><Testing><Therapeutic><Thymotaxin><Translations><United States><Universities><Vaccine Production><Vaccines><Validation><bench bed side><bench bedside><bench to bed side><bench to bedside><bench to clinic><beta-2 Microglobulin><blood stem cell><cell mediated therapies><cell type><cell-based therapy><cellular therapy><chimeric antigen receptor (CAR) T cell therapy><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cell therapy><chimeric antigen receptor T cells><clinical development><clinical practice><clinical translation><cold preservation><cold storage><design><designing><developmental><experiment><experimental research><experimental study><first in man><first-in-human><gRNA><gene modification><hematopoietic progenitor><hematopoietic stem progenitor cell><hemopoietic progenitor><hemopoietic stem cell><innovate><innovation><innovative><mRNA><malignancy><manufacturing facility><manufacturing process><neoplasm/cancer><phase I protocol><phase II protocol><pre-clinical><preclinical><protocol development><scale up><tech development><technology development><thymus derived lymphocyte><β2 Microglobulin>