ANTIIDIOTYPIC T-CELL ACTIVATION IN MULTIPLE-MYELOMA INDUCED BY M-COMPONENT FRAGMENTS PRESENTED BY DENDRITIC CELLS

The monoclonal immunoglobulin (Ig) (M-component secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determin ants (idiotypes; id) that can serve as tumour-specific antigens. The i ntact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity D endritic cells (DC) have attracted attention as the most efficient ant igen-presenting cells and promising adjuvants for immunotherapy in tum ours. In this study the in vitro T-cell response against F(ab')(2) and Fab fragments, heavy and light chains of the hi-component was examine d in five patients with MM clinical stage I. All fragments were able t o stimulate T cells but F(ab')(2) or Fab fragments and heavy chains in duced a stronger response than light chains. DC induced a significantl y stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma ( type-1 T-cell) response was seen in all patients. Both IFN-gamma and i nterleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')(2) fragment and heavy chain can be used for the induction of type-1 antiidiotypic T-cell response for immunotherap y in MM.