The potential of the graft versus leukemia (GVL) effect to cure leukemia is illustrated by the success of adoptive immunotherapy with donor leukocyte infusions (DLI) to treat patients who have relapsed with CML after an allogeneic bone marrow transplant. Understanding the immunologic mechanisms underlying this could lead to a significant advancement in the treatment of leukemia in both children and adults through adoptive immunotherapy. The following hypothesis will be tested in the proposed research project: The therapeutic effect of DLI is mediated by a distinguishable population of donor-derived, MHC- restricted T cells responding to both allogeneic and leukemia-specific stimuli.
Three Specific Aims are proposed: 1) To characterize at cellular and molecular levels the T cell response to a leukemia-specific peptide (bcr-abl) in the absence (autologous) and presence (allogeneic) of various degrees of major and minor histoincompatibility; (2) To characterize at cellular and molecular levels the T cell response to intact CML cells, compare this response to that generated by the bcr-abl peptide, and evaluate how alloreactivity alters these responses; and (3) To assess the repertoire of T cells in the peripheral blood of patients given DLI for CML and compare the in vivo T cell repertoire to that identified in vitro in Specific Aims 1 and 2 to distinguish alloreactive and leukemia-reactive T-cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA077330-02
Application #
2896404
Study Section
Subcommittee G - Education (NCI)
Program Officer
Myrick, Dorkina C
Project Start
1998-09-25
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226