Combinations of the cytokines IL-12, IL-2 and IFN-alpha significantly augment whereas the cytokine IL-4 suppresses the cytokine-induced antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2
D. Flieger et al., Combinations of the cytokines IL-12, IL-2 and IFN-alpha significantly augment whereas the cytokine IL-4 suppresses the cytokine-induced antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2, CYTOKINE, 12(6), 2000, pp. 756-761
Since some cytokines effectively enhance the cytotoxicity of monoclonal ant
ibodies, we investigated whether a combination of cytokines can augment the
antibody-dependent cellular cytotoxicity (ADCC) of monoclonal antibodies 1
7-1A and BR55-2 against the colorectal carcinoma cell line HT29, Since mono
cytes/macrophages are important effector cells for ADCC, we used a new flow
cytometric cytotoxicity assay, which allows the analysis of long-term-ADCC
exerted by these cells. In our previous studies with peripheral blood mono
nuclear cells from normal donors, we found that IL-2, IL-12 and IFN-alpha i
ncrease ADCC, Therefore, we examined whether combination of these three cyt
okines with IL-2, IL-4, IL-6, IL-10, IL12, IFN-alpha, IFN-gamma, GM-CSF, M-
CSF and TNF-alpha may yield higher ADCC than obtained by the application of
single cytokines. Indeed, we found that the combinations IL-2/IFN-alpha, I
L-2/IL-12 and IL-12/IFN-alpha potentiated ADCC. Interestingly, the ineffect
ive single cytokines TNF-alpha and CM-CSF in the combinations IL-2/TNF-alph
a, IFN-alpha/TNF-alpha and IFN-alpha/GM-CSF also proved to enhance ADCC. In
contrast, IL-4 significantly suppressed the IL-2, IL-12 and IFN-alpha-indu
ced ADCC, In addition, the immunosuppressive cytokine IL-10 in higher conce
ntrations significantly suppressed the IL-12-induced-ADCC. Our results may
be useful to find combinations of cytokines and mAb for the treatment of ca
ncer. (C) 2000 Academic Press.