Despite progress in treating canine lymphoma, most affected dogs eventually develop resistance to chemotherapy and succumb to their disease. In human medicine, the ? subunit of the interleukin-2 receptor (IL-2R?) has been developed as a target for Immunotherapy of chemoresistant lymphoma patients. Intensively studied as a molecule present on normal lymphocytes that are activated, IL-2R? has recently been developed as a target on malignant lymphocytes that have been found to express this protein inappropriately. This has been accomplished using anti-IL-2R? monoclonal antibody (Mab) to deliver cellular toxins or radioisotopes directly to the cancer cells, a strategy that overcomes drug resistance. We would now like to develop such an antibody against the canine Il-2R? subunit that could benefit dogs with lymphoma. Our rationale for pursuing this approach stems from molecular data we generated indicating that a high percentage of canine lymphomas from Golden Retrievers and Rottweilers express Il-2R?. Having synthesized canine recombinant (cr) IL-2R? using the gene sequence we cloned, we are now ready to produce and validate Mabs against it. To accomplish these goals, 1) we will employ a novel immunization strategy to prepare murine anti-canine IL-2R? Mabs, 2) develop a test using anti-canine IL-2R? Mabs for the detection of IL-2R? shed into the blood of Golden Retriever and Rottweiler lymphoma patients, and 3) screen lymphoma biopsies from Golden Retrievers and Rottweilers for IL-2R?. Mabs generated to Canine IL-2R? will be a powerful tool in the diagnosis, prognosis, and treatment of canine lymphoma.