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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3280-3285
IMMUNOBIOLOGY
Tumor lysate-specific cytotoxic T lymphocytes in multiple
myeloma: promising effector cells for immunotherapy
Yue-Jin Wen,
Rui Min,
Guido Tricot,
Bart Barlogie, and
Qing Yi
From the Myeloma and Transplantation Research Center,
University of Arkansas for Medical Science, Little Rock.
The idiotype protein, secreted by myeloma plasma cells, is a
tumor-specific but weak antigen. Idiotype-based immunotherapy has been
explored in myeloma patients with disappointing results. It is
conceivable that myeloma cells contain a multitude of tumor antigens
that can more effectively stimulate antitumor T cells. To explore the
possibility of using whole myeloma cells as a source of tumor antigens
for immunotherapy, the current study was undertaken to generate and
examine the function of myeloma-specific cytotoxic T lymphocytes
(CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates
as stimulating cells. After repeated stimulation, specific CTL lines,
containing CD4+ and CD8+ T cells, were
generated from myeloma patients. Our results show that these T cells
not only recognized and lysed autologous myeloma protein-pulsed DCs,
they also killed autologous primary myeloma cells. Occasionally, CTLs
responded to autologous idiotype-pulsed DCs and to allogeneic primary
myeloma cells. No cytolytic activity, however, was detected against
autologous lymphocytes including B cells, suggesting that the T cells
acted specifically against myeloma cells. Cytotoxicity against target
cells was major histocompatibility complex class 1 and, to a lesser
extent, class 2 restricted and was dependent mainly on the
perforin-mediated pathway. CTLs secreted predominantly interferon-
and tumor necrosis factor- on antigenic stimulation, indicating a
type 1 T-cell subset. These findings represent the first demonstration
that tumor cell lysate-primed CTLs kill only myeloma cells, not
autologous lymphocytes. This provides a rationale for myeloma
cell-based immunotherapy in multiple myeloma.

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