Study On The Treatment Of Anti-colon Cancer Mediated By The Combination Of DC Vaccine Loaded With Cancer Stem Cells-derived Antigens And Anti-PD-L1 Antibody

Objective Colon cancer as a common malignant tumor in the digestive tract,the incidence and mortality of colon cancer were increasing year by year in our country.Due to postoperative recurrence,radiotherapy and chemotherapy tolerance and other characteristics,currently the clinical treatment strategies against the colon cancer still always unsatisfactory.Therefore,it needs to explore a new colon cancer treatment strategy.Cancer stem cells(CSCs)are few subpopulations in tumor tissue,with self-renewal ability,infinite proliferation,multidirectional differentiation and insensitive to chemoradiotherapy,which are closely related to tumorigenesis,development and various biological resistance.The theory of tumor stem cell theory has led to the recognition that tumor stem cell as a target of anti-tumor treatment strategy for the complete cure of the tumor has brought possible.Dendritic cells(DC)are currently known as the most powerful in vivo antigen presenting cells(APC),which can specifically induce the immune response of the body.Based on this theory and the development of specific tumor stem cell vaccine for the killing of cancer stem cells possible.PD-L1 plays an important role in the process of tumor immune escape,and anti-PD-L1 monoclonal antibody can inhibit the expression of PD-L1 in tumor microenvironment,thus enhancing the effect of DC vaccine-mediated immunotherapy.Therefore,we sort CD44+ cells as mouse colon cancer stem cells from mouse colon cancer cell line CT-26 with CD44 as the sorting marker,and the DC vaccine,which is intended to be fully antigenized by CD44+ CT-26 mouse colon cancer stem cells,is used in combination with anti-PD-Ll monoclonal antibody.To explore whether this combination therapy can effectively treat colon cancer in mice,and provide new ideas for targeted treatment of colon cancer.Methods CD44+ CT-26 cells were obtained by immunomagnetic beads method and cultured in serum-free DMEM/F12 medium with the 20ng/ml EGF,20ng/ml b FGF and 2% B27.DCs were obtained from mouse bone marrow,CT-26 cell lysates and CD44+ CT-26 cell lysates were used as antigen-loaded DCs to obtain DCCT-26 and DCSC vaccines.Then,the mice were immunized with BALB/c mice with CD44 cells in combination with anti-PD-L1 monoclonal antibody for immunotherapy.In the course of the experiment,the survival status and tumor growth of the mice were recorded,the spleen of the mice was taken to detect the killing effect of the T cells against the colon cancer cells.Results(1)Compared with Control group and ?PD-L1 group,the tumor growth of DCSC+?PD-L1 mice was significantly inhibited(P <0.05),the tumor weight was significantly decreased(P <0.05).(2)Compared with DCSC group,there were no significant differences in other indicators between DCSC+?PD-L1,except the stronger cytolytic activity of the CTL-induced CT-26 cells(P <0.05).(3)Compared with DCCT-26 group,there were no significant differences in other indicators between DCSC,except the smaller of the tumor volume(P <0.05).(4)Compared with DCCT-26+?PD-L1 group,there were no significant differences in other indicators between DCSC+?PD-L1.Conclusion In CT-26 mouse xenograft model,CD44+ CT26 cells completed antigen-pulsed DC vaccine combined with anti-PD-L1 monoclonal antibody could produce effective anti-tumor immune therapy,inhibiting tumor growth,enhancing the killing effect on tumor cells.However,compared with the tumor cell antigen pulsed DC vaccine,the advantage of anti-tumor immune therapy was not obvious.