The Cell Processing laboratory is working to develop and improve cancer cellular therapies including Dendritic Cell (DC) therapies, chimeric antigen receptor (CAR) T cell therapies and T cell engineered to express T cell receptors (TCRs) specific to tumor antigens. The laboratory is working to improve the manufacture of Bone Marrow Stromal Cells (BMSCs) and induced pluripotent stem (iPS) cells for regenerative medicine applications. In addition, the laboratory is developing antigen-specific T cells to treat viral infections in immune suppressed patients. Dendritic cells are an important adjuvant for cancer vaccines. The Cell Processing Laboratory is currently producing DCs expressing HER2/neu to treat cancer patients whose tumors express this antigen. The lab has discovered that factors in the plasma from some people can inhibit the expression of HER2/neu by DCs. The cell processing laboratory has developed and is manufacturing several CAR T cell therapies. CAR T cells expressing CD19, CD19-CAR T cells, are being manufactured in order to treat pediatric patients with B cell leukemia. Manufacturing of CD19-CAR T cells using a humanized CD19 antibody has recently been initiated. These CAR T cells are being used to treat adults with B cell lymphomas. The laboratory has also developed and is manufacturing anti-GD2 CAR T cells to treat patients with sarcoma, anti-B Cell Maturation Antigen (BCMA) to treat patients with multiple myeloma and anti-CD22 CAR T cells to treat patient with CD19-negative B cell leukemia. Human Papillomavirus (HPV) infection is associated with a number of cancers. The laboratory has developed a method to produce T cells that express a T cell receptor (TCR) that is specific for the HPV-16 oncoprotein E7. These cells will be used to treat patients with HPV-associated cervical and oropharyngeal cancers. Bone marrow stromal cells (BMSCs) can inhibit in function and support tissue regeneration Preliminary studies suggest that acute graft versus host disease and autoimmune diseases can be treated with BMSCs. In addition, BMSCs secrete cytokines and growth factor that improve the healing of damaged tissue and BMSCs have used to treat patients with ischemic heart disease and peripheral vascular disease. The Cell Processing Laboratory has developed a bank of BMSCs products collected from healthy subjects that is being used to treat hematopoietic stem transplant patients with acute graft versus host disease or graft failure and inflammatory bowel disease. The lab has also developed a process to produce autologous BMSCs to treat patients with ischemic heart disease. The laboratory has investigated the use of platelet lysate in place of fetal bovine serum as a media supplement to support the growth and expansion of BMSCs. The laboratory has also investigated the effect of the degree of BMSC confluence at the end of the culture period on BMSC properties. The Cell Processing Laboratory is also collaborating with NEI investigators to develop methods to manufacture iPS cells from CD34+ cells isolated from the blood and to differentiate the iPS cells in retinal pigment epithelial (RPE) cells. The RPE cells will be used to treat patients with age related macular degeneration. The laboratory completed the development of a protocol to treat and prevent infections to CMV, EBV, adenovirus and BK virus using multiple virus specific T cells. A protocol to treat patients with progressive multifocal leukoencephalopathy(PML) using BK-specific viral T cells has been developed and patients are being treated.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACL002120-09
Application #
9340948
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
Zip Code
Allen, Elizabeth S; Stroncek, David F; Ren, Jiaqiang et al. (2017) Autologous lymphapheresis for the production of chimeric antigen receptor T cells. Transfusion 57:1133-1141
West, Kamille A; Gea-Banacloche, Juan; Stroncek, David et al. (2017) Granulocyte transfusions in the management of invasive fungal infections. Br J Haematol 177:357-374
Liu, Shutong; de Castro, Luis F; Jin, Ping et al. (2017) Manufacturing Differences Affect Human Bone Marrow Stromal Cell Characteristics and Function: Comparison of Production Methods and Products from Multiple Centers. Sci Rep 7:46731
Stroncek, David F; Ren, Jiaqiang; Lee, Daniel W et al. (2016) Myeloid cells in peripheral blood mononuclear cell concentrates inhibit the expansion of chimeric antigen receptor T cells. Cytotherapy 18:893-901
Anand, Ankit; Anandi, Prathima; Jain, Natasha A et al. (2016) CD34+ selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation. Support Care Cancer 24:815-822
Ali, Syed Abbas; Shi, Victoria; Maric, Irina et al. (2016) T cells expressing an anti-B-cell-maturation-antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood :
Sabatino, Marianna; Hu, Jinhui; Sommariva, Michele et al. (2016) Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood 128:519-28
Merchant, Melinda S; Bernstein, Donna; Amoako, Martha et al. (2016) Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas. Clin Cancer Res 22:3182-91
Stroncek, David F; Tran, Minh; Frodigh, Sue Ellen et al. (2016) Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates. Transfusion 56:511-7
Stroncek, David F; England, Lee (2015) Protecting the Health and Safety of Cell and Tissue Donors. ISBT Sci Ser 10:108-114

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