Multiple Myeloma (MM) is a malignant B cell disorder characterized by the proliferation of atypical plasma cells in the bone marrow and the presence of monoclonal protein in the serum and/or urine. MM remains incurable with either standard dose or high dose chemotherapy. High dose therapy followed by autologous stem cell transplantation may result in higher complete remission rates and improved long-term survival compared to standard chemotherapy. However, relapse of disease is the principal reason for the failure of this approach. Thus, it is imperative that new agents be evaluated in these patients. A promising area for novel therapies is based on enhancement of host anti-myeloma immunity using vaccination. It has been shown that vaccination with Idiotype (Id) or Id-pulsed dendritic cells (DCs) can trigger Id-specific humoral and cellular responses in some patients with myeloma. However, the use of myeloma associated Idiotype as the tumor antigen is limited by several factors. Our laboratory has developed a novel method which involves vaccination with autologous dendritic cells transfected with tumor derived RNA in order to elicit tumor specific cytotoxic T-lymphocyte (CTL) responses. This strategy has been validated in murine models and has been applied in clinical trials in patients with solid tumors. Based on these developments, the primary hypothesis of this proposal is that DCs isolated from patients with MM and transfected with myeloma RNA will be capable of inducing anti myeloma CTL responses. In order to test this hypothesis, a series of pre clinical and clinical studies will be performed which include: 1) optimizing the generation of DCs from patients with MM, 2) optimizing techniques for isolating total tumor RNA from MM sample, 3) determining in vitro whether DCs transfected with myeloma RNA generate potent CTL responses, and 4) conducting clinical trial with DCs transfected with total tumor RNA in patients with MM.
