Dendritic cells coinjected with tumor cells treated with an anticancer drug to induce tumor rejection.

Abstract

We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug was added. CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally (i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally. Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26 cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher level of cytotoxic T-cell activity and interferon-gamma production was seen in the protected mice. When MMC (i.p.) treatment was followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed. DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through the acquisition of tumor-associated antigens from apoptotic tumor cells.