Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells.
Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1-type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell-mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether Id-specific CD8(+) T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer-sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I-restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response. (Blood. 2000;96:2828-2833)
Li
Y
Y
Center for Genetic and Cellular Therapies, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Bendandi
M
M
Deng
Y
Y
Dunbar
C
C
Munshi
N
N
Jagannath
S
S
Kwak
L W
LW
Lyerly
H K
HK
D000328:Adult; D017951:Antigen Presentation; D001402:B-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D020014:K562 Cells; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009194:Myeloma Proteins / Q000276:immunology*
D007130:Immunoglobulin Idiotypes; D008222:Lymphokines; D009194:Myeloma Proteins