The goal of this project is to develop a new method of treatment for Human T cell lymphoma. The T cell receptor made by each malignant T cell tumor is unique and has proven to be an effective target for an immune response. An Animal Model of transplantable T cell lymphoma will be used to perfect methods for vaccination against the T cell receptor and to study the mechanisms of tumor immunity. Specifically, we will develop recombinant adenoviruses for the delivery of transgenes encoding the tumor-derived T cell receptor to the immune system of the host. Various constructs containing the TCR linked to carrier molecules and i immunostimulatory sequences will be compared. Strategies of priming and boosting the immune response will be developed. These adenoviruses will be used to deliver the immunogen of dendritic cells of the host ex vivo and in situ. We will choose the most successful vaccine strategy from the animal model to design and conduct Human Clinical Trials in patients with T cell lymphomas. For these trials we will draw on a defined patient population with cutaneous T cell lymphoma where a dedicated clinic and a close working group of clinical investigators have focused on the disease and its management. The pathologic specimens will be studied in collaboration with other investigators within the problem using DNA microarrays for the analysis of gene expression patterns to gain insights into the biology of the disease and to develop more precise methods of diagnosis and prognostication.
Showing the most recent 10 out of 523 publications
