This Program Project application seeks support for clinical and laboratory studies concerning the major obstacles to successful allogeneic bone marrow transplantation for patients with leukemia. These problems include recurrent malignancy, viral infections and graft versus-host disease. The program consists of one clinical and five experimental projects. These six interrelated projects in the application are supported by two cores, one providing statistical expertise and one for administration and coordination of research. The clinical project deals with novel approaches to eradicate leukemia and to prospectively evaluate drug or drug combinations intended to prevent serious transplant related complications such as graft versus host disease (acute and chronic) and human cytomegalovirus associated interstitial pneumonia. These clinical studies are interrelated with the five experimental projects that will extend our understanding of the problems associated with therapeutic bone marrow allografting. The laboratory projects address biologically important transplant related problems and topics. Studies will be performed the define the antigen specific immune response to HCMV and identify immunodominant antigens. It is also our goal to develop a subunit vaccine that would allow the efficient transfer of HCMV specific T cell immunity from donor to recipient in order to alter the natural history of HCMV infection after BMT. Further characterization of HCMV infection after BMT will be accomplished utilizing molecular biologic methods to characterize the structural components of HCMV matrix proteins and to define their virologic and biologic function. Studies will also be performed to define the role of cytokines in the tissue injury of the lungs of mice and humans with CMV infection. Molecular studies will address genetic aspects of bone marrow transplantation including the cloning and characterization of a DQ-beta gene associated with the development of graft versus host disease. Finally, based on new findings that document the detection of herpes simplex virus in hematopoietic cells of mice and humans, molecular biologic studies will be performed to investigate the nature of this infection and to determine the biological significance of infection of these cell types.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA030206-11
Application #
3093386
Study Section
Special Emphasis Panel (SRC (H1))
Project Start
1981-07-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
11
Fiscal Year
1992
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

Showing the most recent 10 out of 364 publications