Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects

Multiple myeloma (MM) is characterized by a clonal proliferation of maligna nt plasma cells in the bone marrow secreting a monoclonal immunoglobulin (p araprotein) with specific antigenic determinants, the idiotype (Id), which can be regarded. as a tumour-associated antigen (TAA). In order to analyse the impact of a dendritic cell (DC)-based vaccine, 11 patients with advance d MM were treated with CD34 stem cell-derived dendritic cells that were pul sed with Id peptides. Subsequently, the patients received three boost immun izations every other week with a combination of Id and granulocyte-macropha ge colony-stimulating factor (GM-CSP) (nine patients) or with Id peptide-pu lsed dendritic cells again (two patients). The treatment was well tolerated with, no side-effects. The present clinical study was a proof of concept a nalysis of dendritic cell-based vaccines in MM. The capacity of the dendrit ic cells to activate idiotype-specific T cells was verified by in vitro sti mulation experiments before the vaccination therapy. Immunological effects of the Id vaccination were analysed by monitoring changes in anti-idiotype antibody titres and idiotype-specific T-cell activity. After vaccination, t hree out of 10 analysed patients showed increased anti-idiotype antibody se rum titres, indicating the induction of an idiotype-specific humoral immune response. The idiotype-specific T-cell response analysed by ELISpot was in creased in four out of 10 analysed patients after vaccination, and one pati ent: had a decreased plasma cell infiltration in the bone marrow. In conclu sion, five out of 11 patients showed a biological response after vaccinatio n. Thus, our data indicate that immunotherapy with Id-pulsed DCs in MM pati ent's is feasible and safe. DC generated from CD34(+) progenitor cells can serve as a natural adjuvant for the induction of clinically relevant humora l and cellular idiotype-specific immune responses in patients suffering fro m advanced MM.