Effect Of Dendritic Cells Pulsed With Tumor Lysate Antigens Co-cultured With Cytokine Induced Killer Cells On Cytotoxicity Against Drug-resistant Leukemic Cells

Objective The occurrence of multidrug resistance is known for the main barrier of leukemia chemical therapy , We investigated the effect of dendritic cells( DC) pulsed with tumor lysate antigens of K562/ A02 co-cultured with cytokine induced killer(CIK) cells on cytotoxicity against multidrug resistant( MDR) leukemia K562/A02 cells with high expression of p- glycoprotein( P- gp) and sensitive K562 cells. Methods Bone marrow mononuclear cells (BMMNC) isolated from healthy adult donors were induced to obtain CIK cells and DC respectively , then CIK cells were co-cultured with DCs.which were pulsed with tumor lysate of K562/A02 (K562A02-DC).The morphologic features were observed with optical microscopy and expressions of markers typical for both populations were measured using flow cytometry.The cytotoxicity of K562/A02-DC-CIK,DC-CIK and CIK against sensitive K562, multidrug resistant leukemia K562/02 andmammary canaer MCF7 cells were measured with MTT assay respectively.Results After pulsing with tumor lysate antigens of K562/ A02, DCs co-cultured with CIK or DC-CIK cells led to a significant increase of the surface molecule expression and lymphocyte proliferation of both populations and had a significant increase in cytotoxic activity against K562/A02 than K562 tumor cells compared with CIK cells without co-culture,The cytotoxicity CIK cells alone to K562 / A02 and K562 cells was (18.76+0.34) %. (23.67+0.44) %> (32.94+0.44) % and (13.7 +0.27)% . (16.07+0.33)%. (24.39+0.61)% respectively at effector at an effector-to-target ratio of(5:l> 10:1 > 20:1). This effect was significantly enhanced by co-culturing with DCs pulsed with tumor lysate antigens of K562/A02 being (42.9+0.67)%, (49.85 + 0.28) %, (63.36 + 0.46)% and (23.56 + 0.43)%, (26.11 + 0.34) %, (34.46+0.35)%. Conclusions Taken together,this study indicated that DC pulsed with tumor lysate antigens of high expression of p-glycoprotein( P- gp) co-cultured with CIK cells could improve lymphocyte proliferation and enhance the cytotoxic activity Especially,could induced a p-glycoprotein specific anti-leukemic immune.