multi-epitope vaccine approach as a platform to study and manipulate the immune response and overcome tolerance to achieve a successful vaccine-induced anti-leukemia effect. 2. Predicting the Response to Treatment Using Gene Mutation Profiling in Metastatic Melanoma Patients Principal Investigator/Institute

Hematological malignancies are most common in individuals over 60 years who are least responsive to current treatments. Immunotherapy strategies could improve outcome in patients otherwise refractory to standard treatment. Most leukemia associated antigens (LAAs) that could be potential targets of immunotherapy regimens are overexpressed non-mutated self-antigens and as such are likely to induce immunological tolerance. We hypothesize that efficient leukemia vaccination may be achieved, provided that ideal LAA are used and the optimum immunological conditions to overcome tolerance are established. PRAME, Wilms tumor (WT1) and proteinase 3 (PR3) are tumor antigens of particular interest since they are widely expressed in hematological malignancies. We propose to investigate a multi-epitope vaccine approach, combining HLA-A*0201 restricted epitopes derived from PR3, WT1, and PRAME. We will use this multi-epitope vaccine approach as a platform to study and manipulate the immune response and overcome tolerance to achieve a successful vaccine-induced anti-leukemia effect. 2. Predicting the Response to Treatment Using Gene Mutation Profiling in Metastatic Melanoma Patients Principal Investigator/Institute Yardena Samuels, Ph.D., Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), NIH Associate Investigator/Institution Phillip Buckhaults, Ph.D., University of South Carolina School of Medicine Associate Investigator/Institution Patrick Hwu, M.D., University of Texas, M. D. Anderson Cancer Center