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

Abstract

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 idiotype protein in the serum makes immunotherapeutic strategies utilizing this protein to generate an anti-idiotype immune response an attractive prospect. We treated two patients with advanced refractory myeloma with a series of four vaccinations using autologous idiotype-protein pulsed dendritic cells 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 was associated with the production of γ-interferon, indicating a TH-1-like response. Furthermore, one patient developed anti-idiotype IgM antibodies. However, no idiotype-specific cytotoxic T-cell response could be demonstrated. Further investigation is warranted to define the optimal conditions for dendritic cell culture and priming to maximize the anti-tumour immune response.