Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients.
Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B-cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous mono-clonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I-III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-gamma and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9-5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19+ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.
Bergenbrant
S
S
Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Yi
Q
Q
Osterborg
A
A
Björkholm
M
M
Osby
E
E
Mellstedt
H
H
Lefvert
A K
AK
Holm
G
G
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D016898:Interferon-alpha; D015847:Interleukin-4