The goal of the studies detailed in Project I is to improve the outcome of allogeneic hematopoietic cell transplantation for hematologic malignancy. The specific disease entities that we will focus on are acute leukemia and myelodysplasia. The improvement in outcome will be achieved by an integrated investigational approach designed to address the following parameters that impact on outcome; (i) disease relapse, (ii) the incidence and severity of acute and chronic graft-versus-host disease, (iii) the development of CMV-associated disease, and (iv) toxicities directly attributable to the preparative regimen. By conducting clinical and laboratory-based studies designed to minimize the incidence and/or the severity of each of these parameters, significant improvement in the outcome of allogeneic transplantation for patients with acute leukemia and myelodysplasia can be achieved. To this end, we propose five specific aims focused on the four parameters listed above within this project entitled """"""""Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy"""""""". The specific of Project I will be realized in the context of a series of Phase I, II and III clinical trials conducted at City of Hope, in collaboration with the BMT programs of Stanford and the Fred Hutchinson Cancer Research and the Southwest Oncology Group. The five specific aims of Project I are: 1) To determine the significance of minimal residual disease detection by molecular assays on subsequent clinical disease relapse, 2) To pilot adoptive T cell therapy targeting CD19 as a strategy to eradicate molecular post-transplant relapse, 3) To improve the efficacy of chemo- prophylaxis of acute and chronic graft-versus-host disease, 4) To delineate optimal pharmacological prophylaxis of cytomegalovirus infection and pilot novel donor/recipient immunization approaches, and 5) To explore novel preparative regimens with optimized anti-tumor activity and minimized end organ toxicities. Project I will serve as a clinical resource for experimental Projects III and VI and will be supported by Cores A, B, C, D, E and F.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA030206-20
Application #
6492783
Study Section
Project Start
2001-08-27
Project End
2002-03-31
Budget Start
Budget End
Support Year
20
Fiscal Year
2001
Total Cost
Indirect Cost
Name
City of Hope National Medical Center
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Limaye, Ajit P; La Rosa, Corinna; Longmate, Jeff et al. (2016) Plasma IL-10 Levels to Guide Antiviral Prophylaxis Prevention of Late-Onset Cytomegalovirus Disease, in High Risk Solid Kidney and Liver Transplant Recipients. Transplantation 100:210-6
Jonnalagadda, Mahesh; Mardiros, Armen; Urak, Ryan et al. (2015) Chimeric antigen receptors with mutated IgG4 Fc spacer avoid fc receptor binding and improve T cell persistence and antitumor efficacy. Mol Ther 23:757-68
Wang, Xiuli; Wong, ChingLam W; Urak, Ryan et al. (2015) CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells. Clin Cancer Res 21:2993-3002
Mardiros, Armen; Forman, Stephen J; Budde, Lihua E (2015) T cells expressing CD123 chimeric antigen receptors for treatment of acute myeloid leukemia. Curr Opin Hematol 22:484-8
Caruso, Hillary G; Hurton, Lenka V; Najjar, Amer et al. (2015) Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity. Cancer Res 75:3505-18
Israyelyan, A; Goldstein, L; Tsai, W et al. (2015) Real-time assessment of relapse risk based on the WT1 marker in acute leukemia and myelodysplastic syndrome patients after hematopoietic cell transplantation. Bone Marrow Transplant 50:26-33
Wussow, Felix; Chiuppesi, Flavia; Martinez, Joy et al. (2014) Human cytomegalovirus vaccine based on the envelope gH/gL pentamer complex. PLoS Pathog 10:e1004524
Rushworth, David; Jena, Bipulendu; Olivares, Simon et al. (2014) Universal artificial antigen presenting cells to selectively propagate T cells expressing chimeric antigen receptor independent of specificity. J Immunother 37:204-13
Jena, Bipulendu; Moyes, Judy S; Huls, Helen et al. (2014) Driving CAR-based T-cell therapy to success. Curr Hematol Malig Rep 9:50-6
Singh, Harjeet; Huls, Helen; Kebriaei, Partow et al. (2014) A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunol Rev 257:181-90

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