) Increasing evidence suggests that eradication of detectable leukemia cells is necessary for cure and that the rate of reduction of tumor load early during therapy also has prognostic significance. This provides the basis to continue our present prospective studies of detection and quantitation of minimal residual leukemia. We use the rearranged antigen receptor genes as clonal markers for qualitative and quantitative PCR analysis. The hypotheses being tested are that a rapid reduction in leukemic burden will predict for a higher cure rate and that eradication of leukemia cells is necessary for cure.
The aim of these studies is to identify in a timely manner patients at sufficiently high risk of relapse that they are candidates for alternative treatment strategies, such as increased intensity of therapy as outlined in Core 9001, or for novel immune-based strategies as outlined in Project 10. Immune-based strategies are dependent upon identification and exploitation of tumor associated antigens. Antigen receptor rearrangements are not only clonal markers, but also tumor-specific antigens and the idiotypic (Id) structures of immunoglobulin from malignant B cells were the first tumor-specific antigens recognized. However, the role of Id-specific CD8+ cytotoxic T lymphocytes in tumor rejection remains elusive.
We aim to characterize Id specific and other tumor-associated peptides that are targets for a CTL-mediated immune response. Therefore, two specific aims are proposed: 1) to detect and quantitate MRD in children and adults with ALL, and 2) to combine molecular biologic techniques with advances in bioinformatics and cellular immunology to identify and characterize peptides that can be a target of a CTL mediated response. The success of this project is dependent upon the clinical resources provided by Project 4 and all Cores. Identification of novel gene products will be dependent upon Project 8, and also upon Project 5, Project 6 and Project 7. This project is particularly interactive with Project 10, to identify patients at sufficiently high risk to merit experimental treatment approaches but also to identify tumor antigens that can be exploited as a target of a T cell- mediated immune response.
Showing the most recent 10 out of 214 publications
