Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: Promising effector cells for immunotherapy

Yue Jin Wen, Rui Min, Guido Tricot, Bart Barlogie, Qing Yi

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

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-γ and tumor necrosis factor-α 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.

Original languageEnglish (US)
Pages (from-to)3280-3285
Number of pages6
JournalBlood
Volume99
Issue number9
DOIs
StatePublished - May 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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