Combining cetuximab with killer lymphocytes synergistically inhibits human cholangiocarcinoma cells in vitro

Aim: We explored the possibility of combining adoptive immunotherapy with cytokine-activated killer (CAK) cells and the epidermal growth factor receptor monoclonal antibody, cetuximab, as a treatment for cholangiocarcinoma. Materials and Methods: CAK cells were cultured with a highdose of interleukin-2 and anti-CD3 monoclonal antibodies. This cell population contained both activated CD16+/CD56+ (NK) cells and CD3+/NKG2Dhigh+ T-cells. The effect of CAK cells and cetuximab, alone and in combination, on the viability of human cholangiocarcinoma cells was evaluated. Results: Culture of CAK cells alone, but not cetuximab alone, exhibited modest cytotoxicity toward cholangiocarcinoma cells. However, combining CAK cells with cetuximab significantly enhanced cytotoxicity. This enhancement was inhibited by the addition of excess human immunoglobulins, suggesting that antibody-dependent cytotoxicity, mediated by activated NK cells in the CAK cell culture was involved in this mechanism. Conclusion: Cetuximab may be used to enhance CAK cell therapeutic activity in patients with cholangiocarcinoma, by potentiating antibody-dependent cellular cytotoxicity.