Research Project: We propose to genetically modify AML cells to produce molecules that promote potent immune-stimulation. HIV-derived lentiviral vectors can efficiently transduce primary AML cells and promote stable and high levels of transgene expression. Novel self-inactivating (SIN) vectors have been recently developed, providing additional biosafety to the lentiviral vector system. We will employ the SIN-lentivirus to deliver genes encoding immunomodulators that function in various pathways of immune-stimulation (CD80, CD70, GM-CSF, CD40L, FLT3L, IL-4). AML cells expressing a single or a combination of immunomodulators will be evaluated by in vitro assays on their ability to promote T-cell, B-cell, dendritic cell mediated immune responses. The biosafety of the lentiviral vectors will be evaluated by in vitro culture systems. Ultimately, we propose to develop a clinical protocol for immunization of AML patients with irradiated, lentivirus transduced cell vaccines. Long-term, disease-free survival is currently achieved in only approximately 30 percent of patients with AML. Major improvement in long-term survival for AML patients could possibly be achieved by active immunotherapy during remission to eradicate minimal residual disease, thus lowering the risks of relapse.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA087864-03
Application #
6514704
Study Section
Subcommittee G - Education (NCI)
Program Officer
Eckstein, David J
Project Start
2000-09-07
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$156,465
Indirect Cost
Name
University of Southern California
Department
Genetics
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089