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

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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.