Deletion of idiotype (Id)-specific T cells in multiple myeloma

Abstract

Myeloma cells secrete monoclonal immunoglobulin (Ig), called myeloma protein. The variable (V) regions of myeloma proteins are unique to each plasma cell tumor, and therefore contain highly tumor-specific antigenic determinants called idiotopes (Id). T cells with specificity for Id are thought to be of importance in eradication of multiple myeloma. In ongoing clinical trials, myeloma patients are vaccinated against the Id of their own myeloma protein, with the aim of inducing Id-specific T cells. However, this strategy will only succeed if Id-specific T cells are present in patients, and are able to respond. In an experimental animal model, we have shown that Id-specific T cells become progressively deleted as the myeloma protein serum concentration exceeds 50 μg/ml. This indicates that the ability of multiple myeloma patients to respond to Id-vaccination might be seriously handicapped. We suggest that Id-vaccination should be reserved for eradication of minimal residual disease, e.g. after high-dose chemotherapy and stem-cell transplantation.