[Induction of active antitumor immune response by myeloma idiotype protein-pulsed dendritic cells].
OBJECTIVE
Most multiple myeloma (MM) patients could not be cured by high-dose chemotherapy and bone marrow transplantation. This study was designed to investigate in vitro killing effect of tumor-specific cytotoxic T lymphocytes (CTLs) stimulated by idiotype protein (Id)-pulsed dendritic cells (DCs) on autologous MM cells.


METHODS
DCs were generated from peripheral blood monocytes of 6 MM patients using interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). After cultured for 5 days, immature DCs were pulsed with Idû tumor necrosis factor-alpha (TNF-alpha) was added at the 7th day. Id-pulsed DCs were cocultured with autologous T cells for 3 days to induce tumor-specific CTLs. MTT assay was used to detect proliferation of autologous T cells, and evaluate killing effect of CTLs on autologous MM cells.


RESULTS
Mature DCs were successfully induced. Id-pulsed DCs markedly increased proliferation of autologous T cells in a dose-dependent manner; stimulation index (SI) of Id-pulsed DCs was the highest [(39.1+/-6.0)%] when the radio of DCs to T cells was 10:1, which was significantly higher than those of unpulsed mature DCs [(19.3+/-7.7)%], Id-pulsed immature DCs [(15.9+/-6.1)%], and unpulsed immature DCs [(11.4+/-4.9)%] (P < 0.01). Id-pulsed DCs induced anti-MM activity of CTLs in a dose-dependent manner. Unpulsed mature DCs also induced cytotoxicity of CTLs against autologous MM cellsû however, when DC:T was 30:1, killing rate of MM cells was significantly higher in Id-pulsed mature DCs group than in unpulsed mature DCs group [(70.1+/-7.9)% vs. (40.8+/-7.8)%,P < 0.05]. KRN7000-pulsed mature DCs stimulated proliferation of allogeneic T cells in a dose-dependent manner; when DC:T was 1:10, SI was significantly higher in KRN7000-pulsed mature DCs group than in unpulsed mature DCs group [(38.5+/-5.7)% vs. (20.2+/-5.7)%, P < 0.05].


CONCLUSIONS
Mature DCs could be induced and Id with biological activity could be extracted from peripheral blood of MM patients. Id-pulsed DCs could induce antitumor immune response. KRN7000 could improve the immune function of in vitro cultured DCs.
Yin
Xiao-Ran
XR
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P. R. China.
Zhang
Mei
M
Luo
Yun-Ya
YY
Lin
Xiu
X
He
Peng-Cheng
PC
Chen
Li-Mei
LM
Cai
Rui-Bo
RB
Guo
Gui-Li
GL
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D005699:Galactosylceramides; D007130:Immunoglobulin Idiotypes; C103873:KRN 7000