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 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 gamma-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.
Cull
G
G
Department of Haematology, Division of Clinical and Laboratory Sciences, Queensland, Australia. gavincull@hotmail.com
Durrant
L
L
Stainer
C
C
Haynes
A
A
Russell
N
N
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D013601:T-Lymphocytes / Q000473:pathology; D014612:Vaccines / Q000627:therapeutic use*
D000888:Antibodies, Anti-Idiotypic; D014612:Vaccines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor