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


METHODS
CAK cells were cultured with a high-dose of interleukin-2 and anti-CD3 monoclonal antibodies. This cell population contained both activated CD16+/CD56+ (NK) cells and CD3+/NKG2D(high+) 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.


CONCLUSIONS
Cetuximab may be used to enhance CAK cell therapeutic activity in patients with cholangiocarcinoma, by potentiating antibody-dependent cellular cytotoxicity.
Fukuoka General Cancer Clinic, 3-1-1 Sumiyoshi, Hakata-ku, Fukuoka 812-0018, Japan. tmorisaki@cancer-clinic.jp
Takashi
T
Morisaki
Masayo
M
Umebayashi
Akifumi
A
Kiyota
Norihiro
N
Koya
Hiroto
H
Tanaka
Hideya
H
Onishi
Mitsuo
M
Katano
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001650:Bile Duct Neoplasms / Q000276:immunology*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D018281:Cholangiocarcinoma / Q000276:immunology*; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D066298:In Vitro Techniques
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab