Enhanced lytic activity of cytokine-induced killer cells against multiple myeloma cells after co-culture with idiotype-pulsed dendritic cells.
OBJECTIVE
There are numerous reports of in vitro and in vivo usage of dendritic cells (DC) pulsed with idiotype, the tumor-specific antigen of multiple myeloma (MM), for immunotherapy of MM. Data suggest that not only T-cells, but also the innate immune system reacts against MM. Here, we examined the cytotoxic activity of cytokine-induced killer (CIK) cells against myeloma cells. This heterogeneous effector population consists of T-, NK- and NKT-cells.


METHODS
CIK cells generated from buffy coats or blood from patients with MM were co-cultured with autologous idiotype-pulsed DC. The cytotoxic activity was investigated in lactate dehydrogenase release assays against cell lines or autologous CD138 positive cells from bone marrow.


RESULTS
CIK cells were able to lyse MM cells at low effector to target ratios. This effect was significantly enhanced by co-culturing with specifically pulsed DC (83.8% lysis at an effector to target ratio of 16:1). Using an interferon-g secreting MACS separation assay, the cytotoxic activity of CIK cells was enhanced to maximal lysis at the lower effector to target ratio of 5:1. High cytotoxic activity was also shown in a completely autologous setting against enriched CD138+ cells from a patient with MM (54.4% lysis at an effector to target ratio of 6:1). Interestingly, there was no cytotoxic activity against the CD138- fraction of the bone-marrow.


CONCLUSIONS
Using a heterogeneous population of effector cells, we were able to activate the innate and the adoptive immune-system against myeloma cells. CIK cells showed high lytic activity against MM cells, which could be enhanced by co-culturing with antigen-specific pulsed DC.
Märten
A
A
Medizinische Universitätsklinik und Poliklinik I, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Renoth
S
S
von Lilienfeld-Toal
M
M
Buttgereit
P
P
Schakowski
F
F
Glasmacher
A
A
Sauerbruch
T
T
Schmidt-Wolf
I G
IG
D000951:Antigens, Neoplasm / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D009194:Myeloma Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016207:Cytokines; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins