Effect of the novel immunomodulator composed of muramyl dipeptide and anti-CD10 monoclonal antibody on dendritic cells in children with acute leukemia

Abstract

Objective To study the effect of a new immunomodulator composed of muramyl dipeptide(MDP) and anti-CD10 monoclonal antibody (MDP-Ab) on the dendritic cells(DC) of children with acute leukemia. Methods DC was adopted to divide the children with acute lymphoblastic leukemia into 6 groups, including the control group, unconjugated anti-CD10 alone, unconjugated MDP alone, MDP-Ab alone, lipopolysaccharide (LPS) alone and MDP-Ab + LPS.The immunophenotypes, the endocytosis interleukin-12 (IL-12) were detected.The stimulation index of autologous lymphocytes was assayed by adopting 5-(and 6)-carboxyfluorescein diacetate, succinimidyl ester(CFSE)-staining method.The supernatants of DC and autologous lymphocytes were used to detect the level of interferon-γ(IFN-γ) by using enzyme-linked immunosorbent assay. Results (1) DC immunophenotype: The expressions of human leukocyte antigen-DR(HLA-DR), mature molecule (CD83) and co-stimulatory molecules (CD80 and CD86) were increased significantly upon DC triggered with MDP-Ab, compared with the control group, unconjugated anti-CD10 group, and unconjugated MDP group, but lower than those in LPS and combination of MDP-Ab with LPS(F=629.62, P=0.000). (2) The level of IL-12: a significant increase in IL-12 level was detected in MDP-Ab group, LPS group, and combination of MDP-Ab with LPS group, compared with the control group, unconjugated anti-CD10 group, and unconjugated MDP group (F=857.87, P=0.000). There were significant differences among the first three groups. (3) Endocytosis assay: The uptake of DCs stimulated by unconjugated anti-CD10, unconjugated MDP, MDP-Ab immunoconjugate, LPS or combination was lower than that of immature DC in the control group which was (81.3±10.1)%. (4)Mixed lymphocyte reaction and IFN-γ level: DC, treated with MDP-Ab, LPS and combination, stimulated more CFSE positive cells and higher level of IFN-γ secretion than the control group and unconjugated anti-CD10 group, unconjugated MDP group. The most significance was observed in combination of MDP-Ab with LPS(F=393.36, P=0.000; F=2 497.18, P=0.000). Conclusion It is concluded that MDP-Ab could promote the proliferation and maturation of DC derived from blood of children with acute leukemia. Key words: Cancer vaccine; Anti-CD10 monoclonal antibody; Muramyl dipeptide; Dendritic cells; Leukemia; Child