In vitroPriming of Myeloma Antigen-specific Allogeneic Donor T Cells with Idiotype Pulsed Dendritic Cells

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Abstract
In vitro priming of T cells with dendritic cells (DC) pulsed with clinically relevant, but weak antigens such as tumor idiotype (Id), is an attractive strategy to generate tumor-specific T lymphocytes. In order to enhance the specific antitumor effect of allogeneic stem cell grafts, we investigated whether induction of tumor specific T cells using autologous DC pulsed with patient's myeloma Id could be maintained and potentiated by in vitro priming. For induction of T cells, DC (5×105/well) were cultured with autologous nonadherent cells (DoNA) (5×106/well) and antigen (TT10 ug/ml, KLH 100 ug/ml and Id 100 ug/ml). The T cells were restimulated every 8–10 days with the corresponding antigen and autologous DC. After 2–4 cycles of in vitro priming, the T cells were compared with nonadherent cells obtained after 2 h attachment on day 0 (DoNA) for antigen-specific cytokine production. In vitro primed T cells (2–4 cycles of stimulation with Ag and DC) showed significant antigen-specific cytokine responses (IFN-γ, TNF-α, GM-CSF) to TT. Similarly, in vitro priming of T cells to Id-pulsed DC resulted in marked increases in cytokine production for both myeloma Id proteins tested. These data suggest that multiple in vitro immunization using DC could be beneficial in generating tumor specific T cells from normal donor PBMC, which may be used for adoptive immunotherapy (e.g. “tumor-specific” donor lymphocyte infusion) of B cell malignancies. In vitro immunization may also offer an alternative to immunization of healthy stem cell transplant donors with tumor antigen.