These proposed studies will attempt to enhance anti multiple myeloma immunity in two ways: 1) induction of myeloma-specific cytotoxic T-lymphocytes, immune cells that act as the most potent immune effectors in the body using vaccine strategies and 2) augmentation of the activity of patients' natural killer cells against myeloma with immunomodulatory drugs including thalidomide, thalidomide analogues, and arsenic trioxide. These investigations provide the framework for novel immune-based strategies to overcome drug resistance and improve patient outcome in myeloma.