Cetuximab +/- chemotherapy enhances dendritic cell-mediated phagocytosis of colon cancer cells and ignites a highly efficient colon cancer antigen-specific cytotoxic T-cell response in vitro

Cetuximab is a human/mouse chimeric IgG1 mAb to EGFR, approved for colorectal carcinoma treatment in combination with chemotherapy. The immune-mediated effects elicited by its human Fc moiety might critically contribute to the overall anti-tumour effectiveness of the antibody. We therefore, investigated cetuximab ability to promote colon cancer cell opsonisation and phagocytosis by human DCs that are subsequently engaged in antigen-cross presentation to CTL precursors. Human colon cancer cell lines were evaluated for susceptibility to DC-mediated phagocytosis before and after treatment with chemotherapy +/- cetuximab in vitro. Human DCs loaded with control or drug-treated cetuximab-coated colon cancer cells, were used to in vitro generate cytotoxic T cell clones from PBMCs of HLA-A(*)02.01(+) donors. T-cell cultures were characterized for immune-phenotype and tumour-antigen specific CTL activity. The results confirmed that treatment of tumour cells with irinotecan+L-folinate+5-flurouracil (ILF) or with gemcitabine+ILF (GILF) increased tumour antigen expression. Moreover, malignant cells exposed to chemotherapy and cetuximab were highly susceptible to phagocytosis by human DCs, and were able to promote their activation. The consequent DC-mediated cross-priming of antigens derived from mAb-covered/drug-treated cancer cells elicited a robust CTL anti-tumour response. On the basis of our data, we suggest a possible involvement of CTL-dependent immunity in cetuximab anti-cancer effects.