H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.
Myelodysplastic syndromes (MDS) are characterized by defective blood formation and high risk for leukemia development and primarily occur in individuals over the age of 65 years old. New strategies of treatment are needed for age-related diseases such as MDS as the US population ages. For tumor vaccine therapies to produce clinical responses in MDS and in cancer patients, appropriate antigen selection, intact antigen presentation, and T-cell function are all critical. We propose a new humanized mouse model in which to study specific questions generated from preliminary data in the parent grant application to decipher the combined effects of lenalidomide and cellular vaccines. We believe that this new treatment strategy is best tested in the setting of high-risk MDS that generally have poor survival, limited treatment options, and who may have a clinical response to the drug alone. Mechanistic studies will aide our understanding of T-cell immunity and improve our ability to utilize this form of immunotherapy and other forms for the treatment of cancer in general. The supplemental work fits the overall scope of the parent project (i.e., development of a therapeutic vaccine in MDS), the project will provide rigorous evaluation for a novel treatment to be applied to a specific human disease (i.e., MDS), the work proposed can be accomplished within a two-year period, the work will generate a novel resource (i.e., xenograft model applicable for future drug discovery efforts in MDS), increases hours for part-time staff, enables the hiring of new staff, retains current personnel, and contracts new key personnel with important skills necessary to complete these new aims.