[Coculture of dendritic cell with cytokine-induced killer results in a significant increase in cytotoxic activity of CIK to tumor cells in vitro and in vivo].
OBJECTIVE
To explore whether coculture of dendritic cells (DC) with cytokine-induced killer (CIK) lead to an increase of cytotoxicity against tumor cells in vitro and in vivo.


METHODS
DC and CIK were prepared from human peripheral blood mononuclear cells (PBMC) by conventional methods, the DC pulsed with or without NB4 leukemia cell lyses (LCL) was cocultured with the CIK (LCL-DC + CIK and DC + CIK), CIK was used as control. Cells phenotypes were analyzed by flow cytometry, secretion of IFN-gamma was determined by ELISPOT assay, and cytotoxicity was assayed in vitro with (51)Cr-release assay. A human leukemia cell NB4-bearing nude mice model was established to test in vivo antitumor efficacy and cell homing.


RESULTS
Compared with CIK, LCL-DC + CIK got a significant increasing of proliferation rate [(18.2 +/- 2.1) times vs (11.6 +/- 2.3) times, P < 0.05] and CD(3)(+)CD(56)(+) expression rate [(51.05 +/- 2.63)% vs (30.18 +/- 1.45)%, P < 0.05], and the number of IFN-gamma secreting cells was increased significantly [(13.86 +/- 3.28)/10(4) cells vs (8.74 +/- 2.53)/10(4) cells, n = 12, P < 0.05]. Meanwhile, LCL-DC + CIK led to an increase of cytotoxic activity to NB4, K562, and KG1a cells, and showed significant inhibition of the growth of transplanted tumor cells and increased tumor free survival rate of nude mice (100% vs 66.7%, P < 0.05), DiI labeled LCL-DC + CIK were detected in spleen, lymph node and tumor within a week after injection. There was no significant different in antitumor activity between LCL-DC + CIK cell and DC + CIK cell.


CONCLUSIONS
Coculture of CIK with DCs can promote the effect of CIK against tumor in vitro and in vivo. DC-CIK is promising as an immuno-therapeutic strategy for patients with leukemia.
Ge
Wei
W
The State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Li
Chang-hong
CH
Zhang
Wei
W
Han
Qin
Q
Deng
Wei-min
WM
Chen
Lei
L
You
Sheng-guo
SG
Zhao
Chun-hua
CH
D000818:Animals; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
D016207:Cytokines