This Program Project Grant application seeks support for clinical and experimental studies concerning the major obstacles to successful allogeneic and autologous stem cell transplantation for the treatment of hematologic malignancies. These problems include recurrence of the underlying disease, graft-versus-host disease and infectious with cytomegalovirus. The program consists of two clinical and four experimental projects that are supported by six cores. The two clinical projects propose studies designed to eradicate leukemia and lymphoma utilization innovations in the preparatory regimen as well as in the treatment of minimal residual disease following either allogeneic and lymphoma antigens in the preparatory regimen of patients undergoing allogeneic for leukemia and myelodysplasia or autologous transplantation for lymphoma. It is also the goal of our studies to use antigen-specific cytolytic T cells in the treatment of minimal residual disease in patients undergoing autologous transplantation for B cell lymphoma and allogeneic transport for Ph+ ALL. Two transplant studies involve genetic manipulation of hematopoietic cells to convey resistance to HIV in patients with HIV-related lymphoma utilizing adeno-associated virus and lentiviruses. Studies will also continue on the prevention of graft-versus- host disease and will develop novel immunologic strategies to prevent cytomegalovirus disease after allogeneic transplantation. The two clinical projects in allogeneic and autologous transplantation serve as a resource for the experimental projects in the program. The four experimental projects address biologically important questions related to transplantation including acquisition of immunity to CMV, the development of antigen-specific cytolytic T cells, treatment of minimal residual disease after autologous and allogeneic transplantation, and genetic modification of stem cells to induce HIV resistant immune reconstitution. These projects attempt to bring laboratory based innovative concepts to clinical use in the treatment of Administration for the coordination of research, Biostatistics, Cellular and Molecular Correlative studies, radioimmunotherapy, Long-Term Follow-Up and a new Biomedicine Production Facility for the production of antibodies, antigen specific cells and viral vectors to be used in the experimental studies proposed in this grant.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Subcommittee G - Education (NCI)
Program Officer
Wu, Roy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
City of Hope/Beckman Research Institute
United States
Zip Code
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

Showing the most recent 10 out of 364 publications