Identification of functionally distinct leukocyte subpopulations combined with the recognition of the roles played by their surface proteins have created new opportunities for hematopoietic reconstitution and immune modulation, and provide the underlying rationale for this program project application. The proposed program brings together the collective expertise of investigators who have identified cell surface molecules that mediate immunomodulatory and alloimmune effects, developed techniques for isolating and activating rare types of mononuclear leukocytes, and demonstrated their therapeutic effects in model systems. The objective of our program is to utilize these discoveries to develop more effective immune cell based therapies, both autologous and allogeneic, for disorders ranging from malignancies to autoimmune disorders and graft-versus-host disease (GVHD). Four projects are described. Two of these projects seek to exploit the immunotherapeutic potential of dendritic cells pulsed with tumor derived antigens; one focuses on a treatment for malignant lymphoma a tumor of hematopoietic origin. while the other focuses on colorectal carcinoma a solid tumor. Two additional projects address novel approaches to the treatment and prevention of GVHD. One addresses the dual role of a polymorphic cell surface molecule, CD3 1, which appears to play an important pathogenetic role in GVHD; the other focuses on the ontogeny and mechanism of action of immunoregulatory CD3+,CD4-, CD8- T cell's derived from bone marrow. Supporting these projects are two cores, including an administrative and biostatistical core that will provide budgetary oversight, assistance in protocol design and statistical analysis and a flow cytometry core that will provide surface phenotype analysis and cell sorting capabilities. We believe that this interdisciplinary and highly interactive program will ultimately lead to the development of new and more potent forms of cell based immunotherapies for a variety of life-threatening disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL057443-01
Application #
2030689
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1996-12-16
Project End
2001-11-30
Budget Start
1996-12-16
Budget End
1997-11-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Stanford University
Department
Pathology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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