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Immature dendritic cell/tumor cell fusions induce potent antitumour immunity
Author(s) -
Takeda A.,
Homma S.,
Okamoto T.,
Kufe D.,
Ohno T.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01194.x
Subject(s) - immunity , cell mediated immunity , dendritic cell , cancer research , cell , immunology , immune system , medicine , biology , genetics
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. Materials and 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‐A b , 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. Conclusion Dendritic cells from tumour‐bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/tumour cell fusion vaccines.