Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma

Myeloma cells produce immunoglobulin which is unique to the malignant clone and presents antigenic determinants, or idiotypes, which may function as a tumour-specific antigen. The availability of significant quantities of idi otype protein in the serum makes immunotherapeutic strategies utilizing thi s protein to generate an anti-idiotype immune response an attractive prospe ct. We treated two patients with advanced refractory myeloma with a series of four Vaccinations using autologous idiotype-protein pulsed dendritic cel ls combined with adjuvant GM-CSF. The vaccinations were well tolerated with a mild fever post-vaccination in one patient. An idiotype-specific T-cell. proliferative response developed in both patients. This T-cell response wa s associated with the production of gamma-interferon, indicating a TH-1-lik e response. Furthermore, one patient developed anti-idiotype IgM antibodies . However, no idiotype-specific cytotoxic T-cell response could be demonstr ated, Further investigation is warranted to define the optimal conditions f or dendritic cell culture and priming to maximize the anti-tumour immune re sponse.