Core C: Cell Processing Resource will support each of the four research projects in this grant proposal by providing three specific services. First. Core C will support process development and pre-clinical translation activities, and provide investigators access to the necessary qualified manufacturing facilities, trained staffing, validated equipment and cGMP expertise required for the therapeutic production of the high affinity WT-1 reactive T-cell populations described in Project 3 and the chimeric antigen receptor transduced T-cells detailed in Project 4. This will include evaluating new equipment and technologies, developing novel procedures, and validating any changes to existing processing and quality control assays prior to implementation. Second, the Core will perform flow cytometry staining and analyses for expression of cell surface markers such as HLA-DP in donor peripheral blood in support of Project 1;hematopoietic progenitor cells, B-cells. Monocytes, NK, NKT, and T-cell subsets including helper, suppressor/killer, regulatory, naive and memory fractions to characterize donor PBSC collections and pre/post-treatment patient specimens (Project 2). Such data, when combined with patient outcome results from Core D long-term follow-up, Core B molecular diagnostic, and analyzed by sophisticated statistical methods provided by Core A, will prove to be extremely useful in correlating which cell subsets within the transplant collections are associated with specific clinical outcomes. These results will help to stimulate development of novel graft engineering approaches and techniques that could further improve allogeneic transplantation outcomes. Third, Core C will assist in the procurement of research samples, and will then process, cryopreserve, and distribute those specimens for research studies. These will include donor and patient peripheral blood and/or bone marrow samples, including pre-transplant, post treatment with novel agents (Project 2), and post-relapse (Projects 2, 3, 4). Such research samples have been extensively utilized in the past, and will continue to be useful in defining mechanisms involved in immune reconstitution. relapse, and the development of GvHD that are the main focus areas of this grant application.

Public Health Relevance

Core C is helping to advance cancer therapy by examining associations of specific cell types and the expression of certain surface markers with transplant outcomes, by obtaining and helping to analyze research specimens by molecular and genetic testing to study mechanisms of relapse and development of GvHD, and by supporting the production of novel, more effective, immune cells capable of eradicating residual disease in the patient.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA018029-37A1
Application #
8368297
Study Section
Special Emphasis Panel (ZCA1-GRB-T (M1))
Project Start
1997-12-22
Project End
2017-06-30
Budget Start
2012-09-25
Budget End
2013-06-30
Support Year
37
Fiscal Year
2012
Total Cost
$328,310
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Walter, R B; Gyurkocza, B; Storer, B E et al. (2015) Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 29:137-44
Walter, Roland B; Sandmaier, Brenda M; Storer, Barry E et al. (2015) Number of courses of induction therapy independently predicts outcome after allogeneic transplantation for acute myeloid leukemia in first morphological remission. Biol Blood Marrow Transplant 21:373-8
Mielcarek, Marco; Kirkorian, Anna Yasmine; Hackman, Robert C et al. (2014) Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation. Transplantation 98:563-8
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Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim et al. (2014) Bacterial foodborne infections after hematopoietic cell transplantation. Biol Blood Marrow Transplant 20:1856-61
Li, Xiang; Deeg, H Joachim (2014) Murine xenogeneic models of myelodysplastic syndrome: an essential role for stroma cells. Exp Hematol 42:4-10
Fisher, C E; Stevens, A M; Leisenring, W et al. (2014) Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis. Transpl Infect Dis 16:505-10
Raj, Kavita; Pagliuca, Antonio; Bradstock, Kenneth et al. (2014) Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant 20:890-5

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