IDIOTYPE IMMUNIZATION COMBINED WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN MYELOMA PATIENTS INDUCED TYPE-I, MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED, CD8-SPECIFIC AND CD4-SPECIFIC T-CELL RESPONSES

Idiotypic structures expressed on the myeloma Ig protein might be rega rded as a tumor-specific antigen. Five patients with IgG myeloma were immunized with the purified serum M-component by repeated intradermal injections together with soluble granulocyte-macrophage colony-stimula ting factor (GM-CSF). All patients developed an idiotype (Id)-specific T-cell immunity, defined as brood T cells predominantly secreting int erferon-gamma (IFN-gamma) and interleukin-2 (IL-2) (type I cells). Id- specific DNA synthesis was induced in one patient. Delayed-type hypers ensitivity against the Id was not evoked. The specific IFN-gamma/lL-2 T-cell response was inhibited (46% to 100%) by a major histocompatibil ity complex (MHC) class I monoclonal antibody (MoAb) in all five patie nts. A 5% to 37% inhibition by an MHC class II MoAb was seen in four p atients. CD4(+) as well as CD8(+) T cells enriched by magnetic microbe ads contained Id-specific cells. The T cells recognized peptides corre sponding to the complementarity-determining regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B cells producin g IgM anti-idiotypic antibodies in all patients. The results indicate that immunization of myeloma patients using the autologous M-component and soluble GM-CSF may evoke an Id-specific predominantly NHC class I -restricted type I T-cell response. (C) 1998 by The American Society o f Hematology.