Patients with multiple myeloma are seldom cured by conventional chemotherapy. High dose therapy with bone marrow transplantation can cure some patients, but despite significant cytoreduction there continues to be a high risk of posttransplant relapse. Additional non-toxic therapies are needed and the induction of an immune response to the tumor Id in the posttransplant setting of minimal residual disease may provide such an approach. The idiotype (Id) of the tumor Ig of B cell malignancies can be recognized by the immune system as a tumor- specific antigen. Myeloma cells, B cells and antigen presenting cells can process and present fragments of the Id on MHC class I or II molecules which can be recognized by T cells. Preclinical studies of id immunization demonstrate that this approach can induce anti-id antibodies and Id-specific T cells which prevent tumor relapse or progression in lymphoma and myeloma models. We will test whether a series Of immunizations with autologous Id-KLH/IGM-CSF can induce Id-specific T cell responses in post autologous or allogeneic BMT myeloma patients. Patients will be evaluated pre-BMT, post BMT and throughout the immunization schema for Id-specific T cells. The anti-tumor activity of these cells will be tested by cloning, expanding and evaluating there function in vitro. In parallel studies, we will determine and test optimal methods of antigen delivery that favor the induction of a CD8+ Id-specific CTL immune response using a murine model system. These results will be used to direct the next series of clinical trials.
The specific aims of this proposal are: 1. to evaluate the ability of immunization with tumor derived Ig (Id) to induce immune responses in patients with multiple myeloma following autologous or allogeneic bone marrow transplant. 2. To use a well characterized murine lymphoma/myeloma model to evaluate new adjuvants and antigen deliver systems to induce and characterize Id specific T cells.
