The immunogenicity of the new MUC1 DNA vaccine for pancreatic cancer / 中华肝胆外科杂志

ABSTRACT

Objective The development of cancer vaccines deserves experimentation,specifically the immunogenicity of the new MUC1 DNA vaccine for pancreatic cancer.Methods Three strategies were combined to optimize the new MUC1 DNA vaccine.The female C57BL/6 mice were immunized,through tibial muscle injection,with 100 μg of plasmid DNA of the recombinant plasmids (pIRES2-EGFP-3VNTR group,pIRES2-EGFP-3VNTR-C1-144 group,pIRES2-EGFP 3VNTR-mIL-18 group,pIRES2-EGFP-3VNTR-C1-144-mIL-18 group,n=5) for a total volume of 100 μl.Mice inoculated with the empty vector pIRES2-EGFP (EV group,n=5) and normal saline (NS group,n=5) were used as vector and blank controls,respectively.All the mice were immunized again every two weeks.Two weeks after the third immunization,all the mice were euthanized and spleen cells were separated for CTL cytotoxic assay.Results The specific cytolysis percentages of the four groups (pIRES2-EG-FP-3VNTR,pIRES2-EGFP-3 VNTR-C1-144,pIRES2-EGFP-3VNTR-mIL-18,pIRES2-EGFP 3VNTR-C1-144-mIL-18) expressing VNTR were higher than the EV and NS group with the effector/target cells ratio (E/T) from 801 to 201 (P＜0.05).Therefore,it showed a difference among the four groups.After the primary immunization,the OD450 of the serum antibody level specific to MUC1 began to increase in the four groups which contained the gene of VNTR3 (P＜0.05).This suggests that the recombinant plasmids could induce a specific antibody response to MUC1,and showed no remarkable difference among the four groups.IFN-γ serum cytokine among the four groups were higher than that of the EV and NS groups (P＜0.05).There was a significant difference of OD450 between the groups containing mIL-18 pIRES2-EGFP-3VNTR-mIL-18,pIRES2-EGFP-3VNTR-C1-144-mIL-18) and those not (pIRES2-EGFP-3VNTR,pIRES2-EGFP-3VNTR-C1-144,)(P＜0.05).Conclusions In conclusion,all of the four recombinant plasmids could induce MUC1 specific CTL and antibodies responses,and C1-144 and IL-18 could enhance the immunogenicity of plasmids.