IDIOTYPE-SPECIFIC T-CELLS IN MULTIPLE-MYELOMA - TARGETS FOR AN IMMUNOTHERAPEUTIC INTERVENTION

In this paper, the results of some recent studies on idiotype-specific T cells in human multiple myeloma (MM) and monoclonal gammopathy of u ndetermined significance (MGUS) are discussed. By using different in v itro measurements such as H-3-thymidine incorporation and ELISPOT assa y, idiotype-specific T cells have been demonstrated in most of MM and MGUS patients. Based on the cytokine-secretion profiles, idiotype-spec ific T cells were found to comprise both Th1 and Th2 cells. A Th1 type immunity was found preferentially in indolent disease and a Th2-like response predominated in advanced MM, suggesting a specific T-cell reg ulation of the tumor B-cell clone. The mode of T-cell recognition of i d determinants on M-components has been studied. We found that idiotyp e-specific T cells recognized processed id determinants presented by M HC class II (HLA-DR) molecules on APC. B cells were much more efficien t APC than monocytes. With the aim to induce or to amplify an idiotype -specific T-cell response, we have immunized MM patients with the auto logous M-component precipitated in aluminum. Three out of the five pat ients showed an induction of specific cellular and humoral immunity. N evertheless, the role for such immunity in controlling the tumor clone remains to be established.