Immature dendritic cell/tumor cell fusions induce potent antitumour immunity.
BACKGROUND
Maturation of dendritic cells (DCs) is important to induce antigen-specific antitumour immunity in cancer immunotherapy with antigen-loaded DCs. However, DCs from tumour-bearing hosts are immature and functionally defective for antigen presentation. We examined whether DCs from tumour-bearing mice could be an effective part of a DC/tumour cell fusion vaccine.


METHODS
Dendritic cells from healthy (DC-Hs) or MC38 tumour-bearing mice (DC-TBs) were examined for endocytotic capacity of FITC-labelled dextran, antigen-presenting capacity in allogeneic mixed leucocyte reaction (allo-MLR) and expression of I-Ab, CD80, and CD86. Fusion cells (FCs) of DC-Hs or DC-TBs and MC38 cells (FC-Hs or FC-TBs) were generated by treatment with polyethylene glycol (PEG). Mice vaccinated with FC-Hs or FC-TBs were studied for cytolytic activity of splenocytes and suppressive activity against established MC38 pulmonary metastases.


RESULTS
Dendritic cell-TBs showed higher endocytotic capacity and lower antigen-presenting capacity than did DC-Hs, results indicating that DC-TBs are more immature and functionally defective for antigen presentation than are DC-Hs. Expression of surface molecules, however, was almost same between DC-Hs and DC-TBs. Splenocytes from mice immunized with FC-Hs or FC-TBs induced the same high cytolytic activity against MC38 cells. Vaccination of mice with FC-Hs or FC-TBs resulted in the same significant suppressive effect against established pulmonary metastases of MC38.


CONCLUSIONS
Dendritic cells from tumour-bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/tumour cell fusion vaccines.
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology; D002459:Cell Fusion; D015179:Colorectal Neoplasms / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000954:Antigens, Surface; D019496:Cancer Vaccines