Chronic myelogenous leukemia (CML) is a disorder of bone marrow characterized by a prolonged period of relative quiescence that eventually leads to an acute phase of leukemia and death. The only curative form of therapy for CML is an allogeneic bone marrow transplant. Allogeneic transplants are successful in treating CML because of several factors. The conditioning regimen decreases the burden of tumor cells in the recipient and T-lymphocytes and perhaps NK cells from the donor are important in destroying residual leukemia cells left after the conditioning treatment. Whether these T-lymphocytes are specifically recognizing tumor targets or a part of the overall process of graft- versus-host disease is not clear. In this proposal, I plan to produce T cell lines and clones from the donor that specifically recognize the recipient CML cells in vitro. The long-term goals of the project are to elucidate the epitopes presented by the CML cells that are specifically recognized by these T cell clones. I will use molecular techniques to produce CML cDNA libraries that will be screened for recognition by the CML-specific T cell clones. In addition, I will elute peptides off CML cells from class I and class II MHC molecules using acid elution and high performance liquid chromatography. The identification of tumor-specific or tissue-specific epitopes from CML cells may allow for the production of a peptide vaccine as an adjunct to the treatment of this disease. Additionally, the identification of CML-specific T cells may allow for a more rationale approach to the use of the graft-versus-leukemia effect in allogeneic bone marrow transplantation.
