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Idiotype Immunization Combined With Granulocyte-Macrophage
Colony-Stimulating Factor in Myeloma Patients Induced Type I, Major
Histocompatibility Complex-Restricted, CD8- and CD4-Specific T-Cell
Responses
Anders Österborg,
Qing Yi,
Lotta Henriksson,
Jan Fagerberg,
Susanne Bergenbrant,
Mahmood Jeddi-Tehrani,
Ulla Rudén,
Ann-Kari Lefvert,
Göran Holm, and
Håkan Mellstedt
From the Departments of Oncology (Radiumhemmet) and Medicine,
Karolinska Hospital, Swedish Institute for Infectious Disease Control,
Stockholm; and the Department of Experimental Oncology, Uppsala
University, Uppsala, Sweden.
Idiotypic structures expressed on the myeloma Ig protein might be
regarded 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-stimulating factor (GM-CSF). All patients developed an idiotype
(Id)-specific T-cell immunity, defined as blood T cells predominantly
secreting interferon- (IFN-) and interleukin-2 (IL-2) (type I
cells). Id-specific DNA synthesis was induced in one patient.
Delayed-type hypersensitivity against the Id was not evoked. The
specific IFN-/IL-2 T-cell response was inhibited (46% to 100%) by
a major histocompatibility complex (MHC) class I monoclonal antibody
(MoAb) in all five patients. A 5% to 37% inhibition by an MHC class
II MoAb was seen in four patients. CD4+ as well as
CD8+ T cells enriched by magnetic microbeads contained
Id-specific cells. The T cells recognized peptides corresponding to the
complementarity-determining regions 1, 2, and 3 of the heavy chain of
the Id. There was a transient rise of B cells producing 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 MHC class
I-restricted type I T-cell response.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2459-2466
© 1998 by The American Society of Hematology.
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