Influence of cytokines, monoclonal antibodies and chemotherapeutic drugs on epithelial cell adhesion molecule (EpCAM) and Lewis(Y) antigen expression

MoAbs against tumour-associated antigens (TAA) may be useful for the treatm ent of colorectal cancer. Since an increased expression of TAA may lead to enhanced antibody-dependent cellular cytotoxicity we examined whether the c ytokines IL-2, IL-4, IL-6, IL-10, IL-12, interferon-alpha (IFN-alpha), IFN- gamma, granulocyte-macrophage colony-stimulating factor, macrophage colony- stimulating factor and tumour necrosis factor-alpha can influence EpCAM and Lewis(Y) expression on the surface of the colorectal carcinoma cell lines HT29, LoVo and SW480. We found that only IFN-alpha increased significantly whereas IL-4 decreased both EpCAM and Lewis(Y) expression. IFN-gamma signif icantly increased Lewis(Y) expression only. When tumour cells were treated with MoAb, the Lewis(Y)-specific MoAb BR55-2 down-regulated Lewis(Y) antige n expression, whereas MoAb 17-1A, which binds to EpCAM, up-regulated this T AA after 3 days of culture. The cytokines IFN-alpha or IFN-gamma combined w ith MoAb 17-1A enhanced further slightly the expression of EpCAM. In additi onal experiments with chemotherapeutic drugs commonly used for the treatmen t of colorectal cancer, we found that 5-fluorouracil, mitomycin-C and oxali platin up-regulated EpCAM and Lewis(Y) antigen expression. Raltitrexed enha nced Lewis(Y) and down-regulated EpCAM expression, whereas CPT-11 had no in fluence at all. The highest expression for EpCAM on HT29 cells was achieved by the combination of IFN-alpha, 5-fluorouracil and MoAb 17-1A. Our result s may be useful for defining combinations of biological and chemotherapeuti c drugs for the treatment of colorectal cancer. Further trials should evalu ate to what extent these combinations enhance antibody-dependent cellular c ytotoxicity.