Immature dendritic cell/tumor cell fusions induce potent antitumour immunity

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.

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.

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.

Dendritic cells from tumour-bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/tumour cell fusion vaccines.